GRK2

Summary

Gene Symbol: GRK2
Description: G protein-coupled receptor kinase 2
Alias: ADRBK1, BARK1, BETA-ARK1, beta-adrenergic receptor kinase 1, adrenergic beta receptor kinase 1, beta-ARK-1
Species: human

Top Publications

  1. doi Combining resonance energy transfer methods reveals a complex between the alpha2A-adrenergic receptor, Galphai1beta1gamma2, and GRK2
    Billy Breton
    Department of Biochemistry, Institute for Research in Immunology and Cancer, and Groupe de Recherche Universitaire sur le Médicament, Universite de Montreal, Montreal, Quebec, Canada
    FASEB J 24:4733-43. 2010
  2. ncbi The inhibitory gamma subunit of the type 6 retinal cGMP phosphodiesterase functions to link c-Src and G-protein-coupled receptor kinase 2 in a signaling unit that regulates p42/p44 mitogen-activated protein kinase by epidermal growth factor
    Kah Fei Wan
    Department of Physiology and Pharmacology, Strathclyde Institute for Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 ONR, Scotland, United Kingdom
    J Biol Chem 278:18658-63. 2003
  3. pmc Monocyte chemoattractant protein-1-induced CCR2B receptor desensitization mediated by the G protein-coupled receptor kinase 2
    A M Aragay
    Departamento de Biologia Molecular, Centro de Biologia Molecular Severo Ochoa, Universidad Autonoma de Madrid, Campus Cantoblanco, E 28049 Madrid, Spain
    Proc Natl Acad Sci U S A 95:2985-90. 1998
  4. ncbi Interaction with neuronal calcium sensor NCS-1 mediates desensitization of the D2 dopamine receptor
    Nadine Kabbani
    Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania 17033, USA
    J Neurosci 22:8476-86. 2002
  5. ncbi Hypertensive left ventricular hypertrophy: relation to beta-adrenergic receptor kinase-1 (betaARK1) in peripheral lymphocytes
    Sung Ji Park
    Department of Internal Medicine, College of Medicine, Gyeongsang National University, Jinju, Korea
    J Hypertens 22:1025-32. 2004
  6. ncbi Differential effects of CC chemokines on CC chemokine receptor 5 (CCR5) phosphorylation and identification of phosphorylation sites on the CCR5 carboxyl terminus
    M Oppermann
    Department of Immunology, University of Gottingen, 37075 Gottingen, Germany
    J Biol Chem 274:8875-85. 1999
  7. ncbi Mutational analysis of Gbetagamma and phospholipid interaction with G protein-coupled receptor kinase 2
    C V Carman
    Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Biol Chem 275:10443-52. 2000
  8. ncbi Synucleins are a novel class of substrates for G protein-coupled receptor kinases
    A N Pronin
    Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Biol Chem 275:26515-22. 2000
  9. ncbi Regulation of membrane targeting of the G protein-coupled receptor kinase 2 by protein kinase A and its anchoring protein AKAP79
    M Cong
    Howard Hughes Medical Institute, Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 276:15192-9. 2001
  10. ncbi Expression and activity of g protein-coupled receptor kinases in differentiated thyroid carcinoma
    Thierry Métayé
    Biophysics Laboratory, Department of Pathology, Jean Bernard Hospital, BP 577, 86021 Poitiers Cedex, France
    J Clin Endocrinol Metab 87:3279-86. 2002

Research Grants

  1. Shahab A Akhter; Fiscal Year: 2015
  2. GPCR Kinase-2 in TNFalpha Signaling in Macrophages
    Narayanan Parameswaran; Fiscal Year: 2013
  3. Walter J Koch; Fiscal Year: 2015
  4. Howard A Rockman; Fiscal Year: 2016
  5. The Regulation of Plasma Membrane Estrogen Receptor-a Levels by Endocytosis
    Reymundo Dominguez; Fiscal Year: 2012
  6. BARRY S KREUTZ; Fiscal Year: 2014
  7. Transgenic Targeting of Vascular G Protein Signaling
    Karsten Peppel; Fiscal Year: 2010
  8. G-Protein Coupled Receptor Kinase-2 on IgE Signaling in Mast Cells
    Hydar Ali; Fiscal Year: 2012
  9. Walter J Koch; Fiscal Year: 2016
  10. Exploring a Role for beta-Arrestins in Cardiac Injury and Repair
    Anna M Gumpert; Fiscal Year: 2013

Detail Information

Publications260 found, 100 shown here

  1. doi Combining resonance energy transfer methods reveals a complex between the alpha2A-adrenergic receptor, Galphai1beta1gamma2, and GRK2
    Billy Breton
    Department of Biochemistry, Institute for Research in Immunology and Cancer, and Groupe de Recherche Universitaire sur le Médicament, Universite de Montreal, Montreal, Quebec, Canada
    FASEB J 24:4733-43. 2010
    ..analysis revealed that stimulation of the α(2A)-adrenergic receptor (α(2A)AR) leads to the recruitment of GRK2 at a receptor still associated with the Gα(i1)β(1)γ(2) complex. The interaction kinetics of GRKs with Gγ(2) (2...
  2. ncbi The inhibitory gamma subunit of the type 6 retinal cGMP phosphodiesterase functions to link c-Src and G-protein-coupled receptor kinase 2 in a signaling unit that regulates p42/p44 mitogen-activated protein kinase by epidermal growth factor
    Kah Fei Wan
    Department of Physiology and Pharmacology, Strathclyde Institute for Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 ONR, Scotland, United Kingdom
    J Biol Chem 278:18658-63. 2003
    ..complex with c-Src and that stimulation of cells with epidermal growth factor promotes the association of GRK2 with this complex...
  3. pmc Monocyte chemoattractant protein-1-induced CCR2B receptor desensitization mediated by the G protein-coupled receptor kinase 2
    A M Aragay
    Departamento de Biologia Molecular, Centro de Biologia Molecular Severo Ochoa, Universidad Autonoma de Madrid, Campus Cantoblanco, E 28049 Madrid, Spain
    Proc Natl Acad Sci U S A 95:2985-90. 1998
    ..phosphorylation of the receptor and with the transient translocation of the G protein-coupled receptor kinase 2 (GRK2, also called beta-adrenergic kinase 1 or betaARK1) to the membrane...
  4. ncbi Interaction with neuronal calcium sensor NCS-1 mediates desensitization of the D2 dopamine receptor
    Nadine Kabbani
    Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania 17033, USA
    J Neurosci 22:8476-86. 2002
    ..NCS-1-D2 receptor interaction may serve to couple dopamine and calcium signaling pathways, thereby providing a critical component in the regulation of dopaminergic signaling in normal and diseased brain...
  5. ncbi Hypertensive left ventricular hypertrophy: relation to beta-adrenergic receptor kinase-1 (betaARK1) in peripheral lymphocytes
    Sung Ji Park
    Department of Internal Medicine, College of Medicine, Gyeongsang National University, Jinju, Korea
    J Hypertens 22:1025-32. 2004
    ..Left ventricular hypertrophy (LVH) is associated with increased cardiovascular risk and altered sympathetic regulation in hypertension...
  6. ncbi Differential effects of CC chemokines on CC chemokine receptor 5 (CCR5) phosphorylation and identification of phosphorylation sites on the CCR5 carboxyl terminus
    M Oppermann
    Department of Immunology, University of Gottingen, 37075 Gottingen, Germany
    J Biol Chem 274:8875-85. 1999
    ..In permeabilized rat basophilic leukemia CCR5 cells, monoclonal antibodies with specificity for GRK2/3 inhibited RANTES-induced receptor phosphorylation...
  7. ncbi Mutational analysis of Gbetagamma and phospholipid interaction with G protein-coupled receptor kinase 2
    C V Carman
    Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Biol Chem 275:10443-52. 2000
    ..b>GRK2 and GRK3 are selectively regulated in vitro by free Gbetagamma subunits and negatively charged membrane ..
  8. ncbi Synucleins are a novel class of substrates for G protein-coupled receptor kinases
    A N Pronin
    Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Biol Chem 275:26515-22. 2000
    ..We found that all synucleins are GRK substrates, with GRK2 preferentially phosphorylating the alpha and beta isoforms, whereas GRK5 prefers alpha-synuclein as a substrate...
  9. ncbi Regulation of membrane targeting of the G protein-coupled receptor kinase 2 by protein kinase A and its anchoring protein AKAP79
    M Cong
    Howard Hughes Medical Institute, Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 276:15192-9. 2001
    ..Here we show that AKAP79 also regulates the ability of GRK2 to phosphorylate agonist-occupied receptors...
  10. ncbi Expression and activity of g protein-coupled receptor kinases in differentiated thyroid carcinoma
    Thierry Métayé
    Biophysics Laboratory, Department of Pathology, Jean Bernard Hospital, BP 577, 86021 Poitiers Cedex, France
    J Clin Endocrinol Metab 87:3279-86. 2002
    ..b>GRK2 and GRK5 were found as the predominant isoforms in the human thyroid...
  11. ncbi Phosphorylation of the platelet-derived growth factor receptor-beta and epidermal growth factor receptor by G protein-coupled receptor kinase-2. Mechanisms for selectivity of desensitization
    Neil J Freedman
    Department of Medicine Cardiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 277:48261-9. 2002
    ..One such kinase, G protein-coupled receptor kinase-2 (GRK2), is known to mediate agonist-dependent phosphorylation and desensitization of multiple heptahelical receptors...
  12. pmc G protein-coupled receptor kinase 2-mediated phosphorylation of ezrin is required for G protein-coupled receptor-dependent reorganization of the actin cytoskeleton
    Sarah H Cant
    MRC Laboratory for Molecular and Cellular Biology and Department of Pharmacology, University College London, London, WC1E 6BT United Kingdom
    Mol Biol Cell 16:3088-99. 2005
    G protein-coupled receptor kinase 2 (GRK2) phosphorylates and desensitizes activated G protein-coupled receptors (GPCRs). Here, we identify ezrin as a novel non-GPCR substrate of GRK2...
  13. pmc Mdm2 is involved in the ubiquitination and degradation of G-protein-coupled receptor kinase 2
    Alicia Salcedo
    Departamento de Biologia Molecular and Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas Universidad Autonoma de Madrid, Madrid, Spain
    EMBO J 25:4752-62. 2006
    G-protein-coupled receptor kinase 2 (GRK2) is a central regulator of G-protein-coupled receptor signaling...
  14. ncbi Characterization of G-protein coupled receptor kinase interaction with the neurokinin-1 receptor using bioluminescence resonance energy transfer
    Rasmus Jorgensen
    7TM Pharma A S, 2970 Horsholm, Denmark
    Mol Pharmacol 73:349-58. 2008
    ..bioluminescence resonance energy transfer(2) (BRET(2)) measurements between the family A NK-1 receptor and GRK2 and GRK5 as well as their respective kinase-inactive mutants...
  15. pmc EGF transregulates opioid receptors through EGFR-mediated GRK2 phosphorylation and activation
    Yuejun Chen
    Pharmacology Research Center and State Key Laboratory of Medical Neurobiology, Shanghai Medical College and Institutes of Brain Science, Fudan University, Shanghai 200032, China
    Mol Biol Cell 19:2973-83. 2008
    ..that activation of epidermal growth factor receptor (EGFR), a member of receptor tyrosine kinase family, stimulates GRK2 activity and transregulates the function of G protein-coupled opioid receptors...
  16. pmc GRK2 activation by receptors: role of the kinase large lobe and carboxyl-terminal tail
    Rachel Sterne-Marr
    Biology Department, Siena College, Loudonville, New York 12211, USA
    Biochemistry 48:4285-93. 2009
    ..To initiate a study of GRK2 activation, we sought to identify sites on GRK2 remote from the active site that are involved in interactions with ..
  17. doi The G protein coupled receptor kinase 2 plays an essential role in beta-adrenergic receptor-induced insulin resistance
    Ersilia Cipolletta
    Dipartimento di Medicina Clinica, Medicina Clinica, Scienze Cardiovascolari ed Immunologiche, Universita Federico II, Via Pansini 5, 80131 Naples, Italy
    Cardiovasc Res 84:407-15. 2009
    ..The cellular levels of G protein coupled receptor kinase 2 (GRK2) increase during chronic betaAR stimulation, leading to betaAR desensitization...
  18. doi Reduced platelet G protein-coupled receptor kinase 2 in major depressive disorder: antidepressant treatment-induced upregulation of GRK2 protein discriminates between responder and non-responder patients
    Jesus A Garcia-Sevilla
    Laboratory of Neuropharmacology, IUNICS, University of the Balearic Islands, Palma de Mallorca, Spain
    Eur Neuropsychopharmacol 20:721-30. 2010
    ..Previous studies have reported that the basal status of GRK2 is different in brains (upregulation) and platelets (downregulation) of subjects with MDD...
  19. doi Low nociceptor GRK2 prolongs prostaglandin E2 hyperalgesia via biased cAMP signaling to Epac/Rap1, protein kinase Cepsilon, and MEK/ERK
    Niels Eijkelkamp
    Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands
    J Neurosci 30:12806-15. 2010
    ..Here we describe a completely novel mechanism via which nociceptor G-protein-coupled receptor kinase 2 (GRK2) contributes to regulation of inflammatory hyperalgesia...
  20. doi Microglial GRK2: a novel regulator of transition from acute to chronic pain
    Annemieke Kavelaars
    Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands
    Brain Behav Immun 25:1055-60. 2011
    ..In this review, we will summarize recent evidence that a kinase known as G protein-coupled receptor kinase (GRK2) is a key regulator of the transition from acute to chronic inflammatory pain...
  21. pmc Reduced expression of G protein-coupled receptor kinases in schizophrenia but not in schizoaffective disorder
    E R Bychkov
    Department of Pharmacology, Vanderbilt University, Nashville, TN, USA
    Neurobiol Dis 44:248-58. 2011
    ..The data suggest distinct molecular mechanisms underlying schizophrenia and schizoaffective disorder...
  22. pmc Mitochondrial localization unveils a novel role for GRK2 in organelle biogenesis
    Anna Fusco
    Clinical Medicine, Cardiovascular and Immunological Sciences Federico II University, Naples, Italy
    Cell Signal 24:468-75. 2012
    ..such as insulin and insulin like growth factor cause cellular accumulation of G protein coupled receptor kinase 2 (GRK2), which in turn is able to induce insulin resistance...
  23. ncbi Phosphorylation of the N-formyl peptide receptor carboxyl terminus by the G protein-coupled receptor kinase, GRK2
    E R Prossnitz
    Department of Immunology, Scripps Research Institute, La Jolla, California 92037
    J Biol Chem 270:1130-7. 1995
    ..phosphorylated by a neutrophil cytosolic kinase with properties similar to the G protein-coupled receptor kinase, GRK2. Both kinase activities show a lack of sensitivity toward protein kinase A, protein kinase C, and tyrosine kinase ..
  24. ncbi Phosphorylation of phosducin and phosducin-like protein by G protein-coupled receptor kinase 2
    A Ruiz-Gomez
    Departamento de Biologia Molecular and Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid, E 28049 Madrid, Spain
    J Biol Chem 275:29724-30. 2000
    G protein-coupled receptor kinase 2 (GRK2) is able to phosphorylate a variety of agonist-occupied G protein-coupled receptors (GPCR) and plays an important role in GPCR modulation...
  25. ncbi Beta 2-adrenergic receptor stimulated, G protein-coupled receptor kinase 2 mediated, phosphorylation of ribosomal protein P2
    Jennifer L R Freeman
    Howard Hughes Medical Institute and Department of Medicine Cardiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Biochemistry 41:12850-7. 2002
    ..phosphorylating the beta2-adrenergic receptor (beta2AR) and other receptors, G protein-coupled receptor kinase 2 (GRK2) can also phosphorylate tubulin, a nonreceptor substrate...
  26. ncbi Differential interaction of GRK2 with members of the G alpha q family
    Peter W Day
    Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, Pennsylvania 19107, USA
    Biochemistry 42:9176-84. 2003
    ..Recently, it was shown that the G protein-coupled receptor kinase 2 (GRK2) contains an RGS domain that binds to the active form of G alpha(q)...
  27. ncbi Bimodal regulation of the human H1 histamine receptor by G protein-coupled receptor kinase 2
    Ken Iwata
    Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Biol Chem 280:2197-204. 2005
    ..Overexpression of GRK2 promoted H1HR phosphorylation in intact HEK293 cells and completely inhibited inositol phosphate production ..
  28. pmc G protein-coupled receptor kinase 2 (GRK2) modulation and cell cycle progression
    Petronila Penela
    Departamento de Biologia Molecular and Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas Universidad Autonoma de Madrid, Universidad Autonoma, 28049 Madrid, Spain
    Proc Natl Acad Sci U S A 107:1118-23. 2010
    ..G protein-coupled receptor kinase 2 (GRK2) plays a central role in G protein-coupled receptor regulation...
  29. ncbi Feedback inhibition of G protein-coupled receptor kinase 2 (GRK2) activity by extracellular signal-regulated kinases
    J A Pitcher
    Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 274:34531-4. 1999
    ..Here we identify a novel mechanism whereby the activity of GRK2 is regulated by feedback inhibition. GRK2 is demonstrated to be a phosphoprotein in cells...
  30. ncbi G protein-coupled receptor kinase and beta-arrestin-mediated desensitization of the angiotensin II type 1A receptor elucidated by diacylglycerol dynamics
    Jonathan D Violin
    Department of Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 281:36411-9. 2006
    ....
  31. ncbi Phosphorylation of p38 by GRK2 at the docking groove unveils a novel mechanism for inactivating p38MAPK
    Sandra Peregrin
    Departamento de Biologia Molecular and Centro de Biologia Molecular Severo Ochoa, Universidad Autonoma de Madrid, 28049 Madrid, Spain
    Curr Biol 16:2042-7. 2006
    ..We report that GRK2 is a novel inactivating kinase of p38MAPK...
  32. ncbi The solution structure and dynamics of the pleckstrin homology domain of G protein-coupled receptor kinase 2 (beta-adrenergic receptor kinase 1). A binding partner of Gbetagamma subunits
    D Fushman
    Laboratory of Physical Biochemistry, The Rockefeller University, New York, New York 10021 6399, USA
    J Biol Chem 273:2835-43. 1998
    ..This suggests that the C-terminal segment of the PH domain may function to mediate protein-protein interactions with the targets of PH domains...
  33. ncbi Protein kinase C switches the Raf kinase inhibitor from Raf-1 to GRK-2
    Kristina Lorenz
    Institut fur Pharmakologie und Toxikologie, Versbacher Strasse 9, D 97078 Wurzburg, Germany
    Nature 426:574-9. 2003
    ..A physiological role for this mechanism is shown in cardiomyocytes in which the downregulation of RKIP restrains beta-adrenergic signalling and contractile activity...
  34. ncbi The full-length, cytoplasmic C-terminus of the beta 2-adrenergic receptor expressed in E. coli acts as a substrate for phosphorylation by protein kinase A, insulin receptor tyrosine kinase, GRK2, but not protein kinase C and suppresses desensitization whe
    S Doronin
    Department of Molecular Pharmacology, University Medical Center, SUNY Stony Brook, Stony Brook, New York 11794, USA
    Protein Expr Purif 20:451-61. 2000
    ..The Y364 residue of BAC1 was predominantly phosphorylated by the insulin receptor kinase. GRK2 catalyzed modest phosphorylation of BAC1...
  35. ncbi Internalization and down-regulation of human muscarinic acetylcholine receptor m2 subtypes. Role of third intracellular m2 loop and G protein-coupled receptor kinase 2
    H Tsuga
    Department of Neurochemistry, Faculty of Medicine, University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113, Japan
    J Biol Chem 273:5323-30. 1998
    ..in Chinese hamster ovary (CHO-K1) cells stably expressing these receptors and G protein-coupled receptor kinase 2 (GRK2)...
  36. ncbi Vascular beta-adrenergic receptor adenylyl cyclase system in maturation and aging
    M A Gaballa
    Departments of Internal Medicine, Veterans Administration Medical Center and University of Arizona Sarver Heart Center, Tucson, AZ, USA
    J Mol Cell Cardiol 32:1745-55. 2000
    ..With maturation, there was no change in G alpha(i)level. However, beta ARK1 levels were increased (55. 4+/-2.1 v. 40.8+/-0...
  37. pmc Identification of additional members of human G-protein-coupled receptor kinase multigene family
    B Haribabu
    Department of Medicine, Duke University Medical Center, Durham, NC 27710
    Proc Natl Acad Sci U S A 90:9398-402. 1993
    ..termed GPRK5, GPRK6, and GPRK7 in addition to the beta-adrenergic receptor kinase (beta ARK) 1 and 2 isoforms (beta ARK1 and beta ARK2)...
  38. pmc Agonist-selective, receptor-specific interaction of human P2Y receptors with beta-arrestin-1 and -2
    Carsten Hoffmann
    Institute for Pharmacology and Toxicology, Versbacher Strasse 9, D 97078 Wuerzburg, Germany
    J Biol Chem 283:30933-41. 2008
    ..The P2Y(6), P2Y(11), and P2Y(12) receptor internalized only when GRK2 was additionally co-transfected, but beta-arrestin translocation was only visible for the P2Y(6) and P2Y(11) ..
  39. ncbi Hypoxia/ischemia modulates G protein-coupled receptor kinase 2 and beta-arrestin-1 levels in the neonatal rat brain
    Maria Stella Lombardi
    Laboratory for Psychoneuroimmunology, University Medical Center Utrecht, Netherlands
    Stroke 35:981-6. 2004
    ..We analyzed GRK and beta-arrestin expression after cerebral hypoxia/ischemia (HI)...
  40. ncbi Kinetics and Gbetagamma modulation of Ca(v)2.2 channels with different auxiliary beta subunits
    Alon Meir
    Department of Pharmacology, University of College London, UK
    Pflugers Arch 444:263-75. 2002
    ..Furthermore, the activation, amplitude, mean open and closed times and G protein modulation of N-type channels were similar for both beta(1b)- and beta(2a)-subunits...
  41. pmc Altered expression and subcellular distribution of GRK subtypes in the dopamine-depleted rat basal ganglia is not normalized by l-DOPA treatment
    M Rafiuddin Ahmed
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    J Neurochem 104:1622-36. 2008
    ..In the globus pallidus, all four GRK isoforms (GRK2, 3, 5, 6) were reduced in the lesioned hemisphere...
  42. ncbi Regulated expression of G protein-coupled receptor kinases (GRK's) and beta-arrestins in osteoblasts
    R F Spurney
    Division of Nephrology, Department of Medicine, Duke University and Durham VA Medical Centers, Durham, NC 27710, USA
    Calcif Tissue Int 73:153-60. 2003
    ..studies, we investigated expression of GRKs and arrestins in osteoblastic cell lines concentrating on the enzymes (GRK2 and GRK3) and protein co-factors (beta-arrestint 1 and beta-arrestin 2) that play dominant roles in regulating GPCR ..
  43. ncbi The substance P receptor, which couples to Gq/11, is a substrate of beta-adrenergic receptor kinase 1 and 2
    M M Kwatra
    Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710
    J Biol Chem 268:9161-4. 1993
    ..g. alpha 2-adrenergic and cardiac muscarinic) are phosphorylated by beta-adrenergic receptor kinases (beta ARK 1 and beta ARK 2)...
  44. ncbi Dynamin and rab5 regulate GRK2-dependent internalization of dopamine D2 receptors
    K Iwata
    Department of Neurochemistry, Faculty of Medicine, University of Tokyo, Japan
    Eur J Biochem 263:596-602. 1999
    ..in COS-7 cells are internalized in an agonist-dependent manner only when G protein-coupled receptor kinase 2 (GRK2) is coexpressed [Ito, K., Haga, T., Lameh, J. & Sadée, W., (1999) Eur. J. Biochem. 260, 112-119]...
  45. ncbi G protein-coupled receptor kinases, beta-arrestin-2 and associated regulatory proteins in the human brain: postmortem changes, effect of age and subcellular distribution
    Muriel Grange-Midroit
    Clinical Research Unit, Department of Psychiatry, University of Geneva, H U G, Belle Idee, CH 1225 Chene Bourg, Switzerland
    Brain Res Mol Brain Res 101:39-51. 2002
    ..In this study, GRK2, GRK6, beta-arrestin-2 and associated regulatory proteins (Gbeta proteins and protein phosphatase (PP)-2A) were ..
  46. ncbi G protein-coupled receptor kinase regulates dopamine D3 receptor signaling by modulating the stability of a receptor-filamin-beta-arrestin complex. A case of autoreceptor regulation
    Kyeong Man Kim
    Department of Pharmacology, College of Pharmacy, Chonnam National University, Kwang Ju, Korea
    J Biol Chem 280:12774-80. 2005
    ..With reductions in basal GRK2/3 activity, an increase in the basal association of filamin A and beta-arrestin2 with D3R is observed...
  47. pmc Beta-arrestin2-mediated inotropic effects of the angiotensin II type 1A receptor in isolated cardiac myocytes
    Keshava Rajagopal
    Department of Surgery, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 103:16284-9. 2006
    ..Cardiomyocytes from GRK2 heterozygous knockout mice (GRK2(+/-)) exhibited augmented responses to SII in comparison to ANG, whereas those ..
  48. ncbi Changes in the expression of G protein-coupled receptor kinases and beta-arrestin 2 in rat brain during opioid tolerance and supersensitivity
    M A Hurlé
    Department of Physiology and Pharmacology, School of Medicine, University of Cantabria, Santander, Spain
    J Neurochem 77:486-92. 2001
    ..Antinociception was evaluated by the tail-flick test. GRK2, GRK3, GRK6 and beta-arrestin 2 immunoreactivity levels were determined by western blot in brain cortices...
  49. ncbi [GRKs and arrestins: the therapeutic pathway?]
    Thierry Métayé
    Laboratoire de Biophysique, Groupe de Recherche en Endocrinologie Expérimentale et Clinique, CHU de Poitiers, BP577, 86021 Poitiers Cedex, France
    Med Sci (Paris) 22:537-43. 2006
    ..Also, transgenic mice with vascular smooth muscle-targeted overexpression of GRK2 showed an elevated resting blood pressure, suggesting that increase in GRK2 level in humans is involved in ..
  50. ncbi Desensitization of GABA(B) receptor signaling by formation of protein complexes of GABA(B2) subunit with GRK4 or GRK5
    Masato Kanaide
    Department of Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
    J Cell Physiol 210:237-45. 2007
    ..Coexpression of other GRKs including GRK2, GRK3, and GRK6 had no effect on GABA(B) receptor-mediated desensitization processes...
  51. pmc 17beta-estradiol-mediated neuroprotection and ERK activation require a pertussis toxin-sensitive mechanism involving GRK2 and beta-arrestin-1
    Reymundo Dominguez
    Neuroscience Program, University of Southern California, Los Angeles, California 90089 2520, USA
    J Neurosci 29:4228-38. 2009
    ..These results demonstrate that E2-mediated neuroprotection and ERK activation involve ERalpha activation of G-protein- and beta-arrestin-mediated mechanisms...
  52. doi Effects and mechanism of Weinaokang on reperfusion-induced vascular injury to cerebral microvessels after global cerebral ischemia
    Yong Qiu Zheng
    Research Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
    Chin J Integr Med 16:145-50. 2010
    ..To study the effects of the Weinaokang (WNK), the active compounds extracted from Ginkgo, Ginseng, and saffron, on ischemia/reperfusion (I/R)-induced vascular injury to cerebral microvessels after global cerebral ischemia...
  53. doi Effects of chlorpyrifos oxon on M2 muscarinic receptor internalization in different cell types
    Elmar M Udarbe Zamora
    Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma 74078, USA
    J Toxicol Environ Health A 71:1440-7. 2008
    ..Agonist-induced phosphorylation of M2 receptors is mediated by G-protein receptor kinase 2 (GRK2). The active metabolite of the organophosphorus insecticide chlorpyrifos, i.e...
  54. doi Different kinases desensitize the human delta-opioid receptor (hDOP-R) in the neuroblastoma cell line SK-N-BE upon peptidic and alkaloid agonists
    Nicolas Marie
    Universite de Caen, Laboratoire de biologie moléculaire et cellulaire de la signalisation, UPRES EA 3919, IFR 146 ICORE, Avenue Cote de Nacre, 14032 Caen, France
    Cell Signal 20:1209-20. 2008
    ..role of G protein-coupled receptor kinases (GRKs) and by using western-blot experiments we observed that only the GRK2 isoform was expressed in the SK-N-BE cells...
  55. ncbi Inhibition of Galphaq-dependent PLC-beta1 activity by PKG and PKA is mediated by phosphorylation of RGS4 and GRK2
    Jiean Huang
    Medical College of Virginia Campus, Virginia Commonwealth University, PO Box 980551, Richmond, VA 23298, USA
    Am J Physiol Cell Physiol 292:C200-8. 2007
    ..Selective phosphorylation of G protein-coupled receptor kinase 2 (GRK2), which contains a RGS domain, by PKA augmented ACh-stimulated GRK2:Galpha(q)...
  56. ncbi Effects of chronic desipramine treatment on alpha2-adrenoceptors and mu-opioid receptors in the guinea pig cortex and hippocampus
    Cristina Giaroni
    Clinical and Applied Pharmacology Centre, University of Insubria and University of Pavia, via O Rossi n 9, I 21100 Varese, Italy
    Eur J Pharmacol 579:116-25. 2008
    ..levels of expression of alpha(2)-adrenoceptors and mu-opioid receptors, the G protein receptor regulatory kinase, GRK2/3 and signal transduction inhibitory G proteins in synaptosomes of the guinea pig hippocampus and cortex were ..
  57. ncbi GRK2-dependent desensitization downstream of G proteins
    M Jurado-Pueyo
    Departamento de Biologia Molecular and Centro de Biologia Molecular Severo Ochoa, CSIC UAM, Cantoblanco, Madrid, Spain
    J Recept Signal Transduct Res 28:59-70. 2008
    ..In particular, we have characterized that elevated GRK2 levels can reduce CCR2-mediated activation of the ERK MAPK route in a manner that is independent of kinase activity ..
  58. ncbi High efficiency method for gene transfer in normal pituitary gonadotropes: adenoviral-mediated expression of G protein-coupled receptor kinase 2 suppresses luteinizing hormone secretion
    J D Neill
    Department of Physiology and Biophysics, University of Alabama, Birmingham 35294 0005, USA
    Endocrinology 140:2562-9. 1999
    ..Previously, we reported that heterologous expression of GRK2, -3, and -6 in GnRH receptor-expressing COS cells by complementary DNA transfection suppressed GnRH-stimulated ..
  59. pmc The complex G protein-coupled receptor kinase 2 (GRK2) interactome unveils new physiopathological targets
    Petronila Penela
    Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa Consejo Superior de Investigaciones Científicas Universidad Autónoma de Madrid, Universidad Autonoma, Madrid, Spain
    Br J Pharmacol 160:821-32. 2010
    b>GRK2 is a ubiquitous member of the G protein-coupled receptor kinase (GRK) family that appears to play a central, integrative role in signal transduction cascades...
  60. ncbi Sequestration of human muscarinic acetylcholine receptor hm1-hm5 subtypes: effect of G protein-coupled receptor kinases GRK2, GRK4, GRK5 and GRK6
    H Tsuga
    Department of Neurochemistry, Faculty of Medicine, University of Tokyo, Japan
    J Pharmacol Exp Ther 284:1218-26. 1998
    ..m2 receptors) expressed in COS-7 cells is facilitated by coexpression of G protein-coupled receptor kinases 2 (GRK2)...
  61. ncbi Reduced G-protein-coupled-receptor kinase 2 activity results in impairment of osteoblast function
    M Bliziotes
    Portland VA Medical Center, Portland, OR 97201, USA
    Bone 27:367-73. 2000
    ..activation by growth factors in UMR 106-H5 osteoblastic cells stably expressing a dominant negative mutant of GRK2 (K220R)...
  62. ncbi Characterization of lymphocyte beta 2-adrenoceptor signalling in patients with left ventricular volume overload disease
    Nduna Dzimiri
    Cardiovascular Pharmacology Laboratory, Biological and Medical Research Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
    Clin Exp Pharmacol Physiol 29:181-8. 2002
    ..3. In the patient group, GRK2 mRNA was increased by 61% (P < 0.001), GRK3 was increased by 54% (P < 0...
  63. ncbi Arrestin2 expression selectively increases during neural differentiation
    Eugenia V Gurevich
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    J Neurochem 91:1404-16. 2004
    ..Two non-visual arrestins, arrestin2 and 3, and five GRKs (GRK2, 3, 4, 5 and 6) are involved in desensitization of many receptors...
  64. ncbi Beta-arrestin binding to the beta2-adrenergic receptor requires both receptor phosphorylation and receptor activation
    Cornelius Krasel
    Institute for Pharmacology and Toxicology, Versbacher Strasse 9, D 97078 Wurzburg, Germany
    J Biol Chem 280:9528-35. 2005
    ..shown to be mediated by phosphorylation of the agonist-stimulated receptor by G-protein-coupled receptor kinase 2 (GRK2) followed by binding of beta-arrestins to the phosphorylated receptor...
  65. doi Two distinct mechanisms mediate acute mu-opioid receptor desensitization in native neurons
    Vu C Dang
    Pain Management Research Institute and Brain and Mind Research Institute, The University of Sydney, New South Wales 2006, Australia
    J Neurosci 29:3322-7. 2009
    ..The rate and extent of MOR desensitization were unaffected by beta(arr)-2 knock-out. Disruption of GRK2 function via inhibitory peptide introduced directly into neurons also failed to affect desensitization in wild type ..
  66. pmc Agonist-induced endocytosis and receptor phosphorylation mediate resensitization of dopamine D(2) receptors
    Dongim Cho
    Department of Pharmacology, College of Pharmacy, Chonnam National University, Gwang ju 500 757, Korea
    Mol Endocrinol 24:574-86. 2010
    ..b>GRK2-mediated enhancement of the internalization and inhibition of D(2)R signaling did not involve receptor ..
  67. ncbi Desensitization of human renal D1 dopamine receptors by G protein-coupled receptor kinase 4
    Hidetsuna Watanabe
    Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA
    Kidney Int 62:790-8. 2002
    ..Because the renal D1 receptor is desensitized in genetic hypertension, we sought to determine the mechanism(s) of the desensitization of D1 receptors endogenously expressed in renal proximal tubules...
  68. ncbi Targeted inhibition of beta-adrenergic receptor kinase-1-associated phosphoinositide-3 kinase activity preserves beta-adrenergic receptor signaling and prolongs survival in heart failure induced by calsequestrin overexpression
    Cinzia Perrino
    Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
    J Am Coll Cardiol 45:1862-70. 2005
    ..Desensitization and down-regulation of beta-adrenergic receptors (betaARs) are prominent features of heart failure largely mediated by increased levels of betaAR kinase-1 (betaARK1)...
  69. ncbi G protein-coupled receptor kinase 2 involvement in desensitization of corticotropin-releasing factor (CRF) receptor type 1 by CRF in murine corticotrophs
    Kazunori Kageyama
    Department of Endocrinology, Metabolism, and Infectious Diseases, Hirosaki University School of Medicine, Hirosaki, Aomori 036 8562, Japan
    Endocrinology 147:441-50. 2006
    ..We found that GRK2 (but not GRK3) mRNA and protein were expressed in rat anterior pituitary cells and AtT-20 cells (a line of mouse ..
  70. pmc An RNA molecule that specifically inhibits G-protein-coupled receptor kinase 2 in vitro
    Gunter Mayer
    Life and Medical Sciences Bonn, Program Unit Chemical Biology, c o Kekulé Institute for Organic Chemistry and Biochemistry, University of Bonn, Gerhard Domagk Strasse 1, 53121 Bonn, Germany
    RNA 14:524-34. 2008
    ..evolution of ligands by exponential enrichment) to develop RNA aptamers that potently and selectively inhibit GRK2. This process has yielded an aptamer, C13, which bound to GRK2 with a high affinity and inhibited GRK2-catalyzed ..
  71. pmc Cardioprotective effect of histamine H3-receptor activation: pivotal role of G beta gamma-dependent inhibition of voltage-operated Ca2+ channels
    Christopher Morrey
    Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 4896, USA
    J Pharmacol Exp Ther 326:871-8. 2008
    ..The discovery of this H(3)R-signaling step may offer new therapeutic approaches to cardiovascular diseases characterized by hyperadrenergic activity...
  72. ncbi P2Y12 receptor signalling towards PKB proceeds through IGF-I receptor cross-talk and requires activation of Src, Pyk2 and Rap1
    Kristof Van Kolen
    Laboratory of Cellular Biochemistry, Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, B 2610 Wilrijk Antwerpen, Belgium
    Cell Signal 18:1169-81. 2006
    ..In cells transfected with the Gbetagamma-scavenger beta-ARK1/GRK2 or Rap1GAPII, stimulation with 2MeSADP failed to enhance PKB phosphorylation demonstrating that the signalling ..
  73. ncbi Competitive displacement of phosphoinositide 3-kinase from beta-adrenergic receptor kinase-1 improves postinfarction adverse myocardial remodeling
    Antonio Curcio
    Dept of Medicine, Cell Biology, and Molecular Genetics, Duke Univ Medical Center, DUMC 3104, Durham, NC 27710, USA
    Am J Physiol Heart Circ Physiol 291:H1754-60. 2006
    ..Together, these results demonstrate that adverse remodeling of the ventricle after MI can be attenuated by a strategy that prevents recruitment of PI3K to the plasma membrane and restores normal beta-AR function...
  74. ncbi Reduced alpha adrenergic mediated contraction of renal preglomerular blood vessels as a function of gender and aging
    John C Passmore
    Department of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, Kentucky 40292, USA
    J Cell Biochem 96:672-81. 2005
    ..G alpha q GeneChip expression declines while expression of adrenergic receptor kinase (GRK2) and tyrosine phosphatases (TyrP) increase with aging in male rats...
  75. ncbi Down-regulation of GRK2 after oxygen and glucose deprivation in rat hippocampal slices: role of the PI3-kinase pathway
    Maria Stella Lombardi
    Laboratory for Psycho neuro immunology, University Medical Center Utrecht, Utrecht, The Netherlands
    J Neurochem 102:731-40. 2007
    G protein-coupled receptor kinase 2 (GRK2) modulates G protein-coupled receptor desensitization and signaling. We previously described down-regulation of GRK2 expression in vivo in rat neonatal brain following hypoxia-ischemia...
  76. ncbi TGFbeta-induced GRK2 expression attenuates AngII-regulated vascular smooth muscle cell proliferation and migration
    Jimin Guo
    Hormones and Cancer Research Unit, Department of Medicine, McGill University Health Center, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, Canada
    Cell Signal 21:899-905. 2009
    ..Previously, we identified the Gprotein-coupled receptor kinase-2 (GRK2), a key regulatory factor in the desensitization of GPCRs, as a direct downstream target of the TGFbeta signaling ..
  77. ncbi Characterization of the phosphorylation sites involved in G protein-coupled receptor kinase- and protein kinase C-mediated desensitization of the alpha1B-adrenergic receptor
    D Diviani
    Institut de Pharmacologie et Toxicologie, Faculte de Medecine, Lausanne, 1005 Switzerland
    J Biol Chem 272:28712-9. 1997
    ..The observation that overexpression of G protein-coupled kinase 2 (GRK2) could increase agonist-induced phosphorylation of Ser404, Ser408, and Ser410, strongly suggests that these serines ..
  78. pmc Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice
    H A Rockman
    Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Proc Natl Acad Sci U S A 95:7000-5. 1998
    ..These findings implicate abnormal betaAR-G protein coupling in the pathogenesis of the failing heart and point the way toward development of agents to inhibit betaARK1 as a novel mode of therapy...
  79. ncbi Overexpression of wild-type and catalytically inactive forms of GRK2 and GRK6 fails to alter the agonist-induced phosphorylation of the C5a receptor (CD88): evidence that GRK6 is autophosphorylated in COS-7 cells
    M D Milcent
    DBMS Laboratoire de Biochimie et de Biophysique des Systèmes Intégrés UMR 314 CEA CNRS, CEA Grenoble, 17 rue des Martyrs, Grenoble Cedex 9, 38054, France
    Biochem Biophys Res Commun 259:224-9. 1999
    ..Overexpression of the dominant negative mutant GRK2-K220R is often accompanied by an inhibition of the agonist-mediated phosphorylation of G protein-coupled receptors...
  80. ncbi G protein-coupled receptor kinase 6A phosphorylates the Na(+)/H(+) exchanger regulatory factor via a PDZ domain-mediated interaction
    R A Hall
    Howard Hughes Medical Institute, Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 274:24328-34. 1999
    ..GRK6A phosphorylates NHERF efficiently on Ser(289) in vitro, whereas GRK6B, GRK6C, and GRK2 do not...
  81. ncbi G protein-coupled receptor Kinase 2/G alpha q/11 interaction. A novel surface on a regulator of G protein signaling homology domain for binding G alpha subunits
    Rachel Sterne-Marr
    Biology Department, Siena College, Loudonville, New York 12211, USA
    J Biol Chem 278:6050-8. 2003
    ..many GPCRs, short term regulation is initiated by agonist-dependent phosphorylation by GPCR kinases (GRKs), such as GRK2, resulting in G protein/receptor uncoupling...
  82. ncbi Activation of the mitogen-activated protein kinases Erk1/2 by erythropoietin receptor via a G(i )protein beta gamma-subunit-initiated pathway
    Christine Guillard
    Department of Hematology, Institut Cochin, INSERM U567, CNRS UMR 8104, Universite Rene Descartes, 27 rue du Faubourg Saint Jacques, 75014 Paris, France
    J Biol Chem 278:11050-6. 2003
    ..Epo-dependent MAPK activation was also sensitive to the G beta gamma competitive inhibitor beta ARK1-ct (C-terminal fragment of the beta-adrenergic receptor kinase), to the Ras dominant negative mutant RasN17, and ..
  83. ncbi Desensitization and internalization of metabotropic glutamate receptor 1a following activation of heterologous Gq/11-coupled receptors
    Stuart J Mundell
    Department of Pharmacology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK
    Biochemistry 43:7541-51. 2004
    ..In co-immunoprecipitation studies, both glutamate and carbachol increased the association of GRK2 with mGluR1a...
  84. ncbi G protein-coupled receptor kinase 2 mediates endothelin-1-induced insulin resistance via the inhibition of both Galphaq/11 and insulin receptor substrate-1 pathways in 3T3-L1 adipocytes
    Isao Usui
    Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, California 92093 0673, USA
    Mol Endocrinol 19:2760-8. 2005
    ..Recently, we have reported that GRK2 can function as a negative regulator of insulin action by interfering with G protein-q/11 alpha-subunit (Galphaq/11)..
  85. ncbi Differential regulation of corticotropin releasing factor 1alpha receptor endocytosis and trafficking by beta-arrestins and Rab GTPases
    Kevin D Holmes
    Cell Biology Research Group, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada
    J Neurochem 96:934-49. 2006
    ..in cells transfected with G protein-coupled receptor kinase (GRK)3 and GRK6 and decreased in cells transfected with GRK2 and GRK5...
  86. ncbi Phosphorylation-independent attenuation of GPCR signalling
    Stephen S G Ferguson
    J Allyn Centre for Cell Biology, Robarts Research Institute, 100 Perth Drive, PO Box 5015, London, Ontario N6A 5K8, Canada
    Trends Pharmacol Sci 28:173-9. 2007
    ..It has recently become apparent, however, that GRK2-mediated regulation of GPCR responsiveness also involves a phosphorylation-independent component that requires both ..
  87. doi Cardiac hypertrophy in neonatal nephrectomized rats: the role of the sympathetic nervous system
    Siddhartha S Ghosh
    Division of Nephrology, VCU Medical Center, Virginia Commonwealth University, MCV Station, Box 980160, Richmond, VA, 23298 0160, USA
    Pediatr Nephrol 24:367-77. 2009
    ..05), but higher G-protein-coupled receptor kinase-2 (GRK2) expression (p < 0.05)...
  88. pmc Role of helix 8 of the thyrotropin-releasing hormone receptor in phosphorylation by G protein-coupled receptor kinase
    Austin U Gehret
    Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA
    Mol Pharmacol 77:288-97. 2010
    ..agonist-dependent phosphorylation attributable to G protein-coupled receptor (GPCR) kinases (GRKs), particularly GRK2. Like many GPCRs, the TRH receptor is predicted to form an amphipathic helix, helix 8, between the NPXXY motif at ..
  89. pmc GRK2 as a novel gene therapy target in heart failure
    Giuseppe Rengo
    Center for Translational Medicine and George Zallie and Family Laboratory for Cardiovascular Gene Therapy, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USA
    J Mol Cell Cardiol 50:785-92. 2011
    ..dysfunction represents a hallmark abnormality of chronic HF, and increased G protein-coupled receptor kinase 2 (GRK2) levels/activity in failing myocardium is among these alterations...
  90. pmc Level of G protein-coupled receptor kinase-2 determines myocardial ischemia/reperfusion injury via pro- and anti-apoptotic mechanisms
    Henriette Brinks
    George Zallie and Family Laboratory for Cardiovascular Gene Therapy, Center for Translational Medicine, Jefferson Medical College, Thomas Jefferson University, 1025 Walnut Street, Philadelphia, PA 19107, USA
    Circ Res 107:1140-9. 2010
    ..GPCR signaling pathways are regulated by GPCR kinases (GRKs), and GRK2 has been shown to be a critical molecule in normal and pathological cardiac function.
  91. doi Age-related β-adrenergic receptor-mediated vasorelaxation is changed by altering G protein receptor kinase 2 expression
    William E Schutzer
    Portland VA Medical Center, Research Service, 3710 SW US Veterans Hospital Rd, Portland, OR 97239, United States
    Vascul Pharmacol 55:178-88. 2011
    ..One kinase responsible for desensitization is G protein receptor kinase 2 (GRK2). We have shown that GRK expression and activity increases with age in Fischer 344 rat aorta...
  92. doi Beta-arrestin2 as a competitor for GRK2 interaction with the GLP-1 receptor upon receptor activation
    Rasmus Jorgensen
    Hagedorn Research Institute, Måløv, Denmark
    Pharmacology 88:174-81. 2011
    ..we have analyzed the interaction pattern between the glucagon-like peptide-1 (GLP-1) receptor (GLP-1R), βarr2, and GRK2 using bioluminescence resonance energy transfer assays...
  93. pmc GRK2 protein-mediated transphosphorylation contributes to loss of function of μ-opioid receptors induced by neuropeptide FF (NPFF2) receptors
    Lionel Mouledous
    Institut de Pharmacologie et de Biologie Structurale, CNRS Université de Toulouse, UMR 5089, 205 route de Narbonne, 31077 Toulouse Cedex, France
    J Biol Chem 287:12736-49. 2012
    ..Ser-377 cross-phosphorylation and MOP receptor loss of function were mediated by the G protein receptor kinase GRK2. In addition, mass spectrometric analysis revealed that the phosphorylation pattern of MOP receptors was ..
  94. pmc Bidirectional regulation of neutrophil migration by mitogen-activated protein kinases
    Xiaowen Liu
    Department of Dermatology, University of Illinois College of Medicine, Chicago, Illinois, USA
    Nat Immunol 13:457-64. 2012
    ..The extracellular signal-regulated kinase Erk potentiated activity of the G protein-coupled receptor kinase GRK2 and inhibited neutrophil migration, whereas the MAPK p38 acted as a noncanonical GRK that phosphorylated the formyl ..
  95. doi Inhibitor of G protein-coupled receptor kinase 2 normalizes vascular endothelial function in type 2 diabetic mice by improving β-arrestin 2 translocation and ameliorating Akt/eNOS signal dysfunction
    Kumiko Taguchi
    Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa ku, Tokyo 142 8501, Japan
    Endocrinology 153:2985-96. 2012
    ..NO synthase (eNOS) activation is known to be negatively regulated by G protein-coupled receptor kinase 2 (GRK2), it is unclear whether the GRK2 inhibitor would have therapeutic effects...
  96. doi Grk2 is an essential regulator of CXCR7 signalling in astrocytes
    Jana Lipfert
    Medical Faculty, Institute of Anatomy, University of Leipzig, Liebigstr 13, 04103, Leipzig, Germany
    Cell Mol Neurobiol 33:111-8. 2013
    ..We demonstrate that Grk2 mediates signalling of SDF-1/CXCL12-bound CXCR7 as suggested by the finding that SDF-1/CXCL12-induced activation of ..
  97. doi Cocaine potentiates multiple 5-HT2A receptor signaling pathways and is associated with decreased phosphorylation of 5-HT2A receptors in vivo
    Jade M Franklin
    Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, 1251 Wescoe Hall Drive, 3048B Malott Hall, Lawrence, KS, 66045, USA
    J Mol Neurosci 55:770-7. 2015
    ..This phenomenon was associated with reduced levels of G-protein receptor kinase 5 (GRK5), but not GRK2 or RSK2, proteins...
  98. pmc Hypertension-associated C825T polymorphism impairs the function of Gβ3 to target GRK2 ubiquitination
    Zhengyu Zha
    Key Laboratory of Molecular Medicine, Ministry of Education, and Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China Molecular and Cell Biology Lab, Institutes of Biomedical Sciences, Fudan University, Shanghai, China School of Life Sciences, Fudan University, Shanghai, China Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Cell Discov 2:16005. 2016
    ..like other Gβ proteins, binds to DDB1 and assembles a DDB1-CUL4A-ROC1 E3 ubiquitin ligase (CRL4A(Gβ3)) to target GRK2 ubiquitination...
  99. doi Regulatory effects of GRK2 on GPCRs and non-GPCRs and possible use as a drug target (Review)
    Chen Chen Han
    Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti inflammatory and Immune Medicine, Hefei, Anhui 230032, P R China
    Int J Mol Med 38:987-94. 2016
    G protein-coupled receptor kinase 2 (GRK2) is a key member of the G protein-coupled receptor kinase (GRK) family...

Research Grants61

  1. Shahab A Akhter; Fiscal Year: 2015
    ..We have found that G protein-coupled receptor kinase-2 (GRK2), a serine-threonine kinase that phosphorylates and uncouples agonist-occupied 2-ARs, is robustly expressed in CF ..
  2. GPCR Kinase-2 in TNFalpha Signaling in Macrophages
    Narayanan Parameswaran; Fiscal Year: 2013
    ..that macrophage biology is regulated by a serine/threonine kinase, namely, G-protein coupled receptor kinase-2 (GRK2). GRK2 was originally discovered for its role in the phosphorylation of -adrenergic receptor and other GPCRs...
  3. Walter J Koch; Fiscal Year: 2015
    ..Over the last 15 years we have identified a key role for G protein-coupled receptor (GPCR) kinase-2 (GRK2) in the pathophysiology of injured or stressed myocardium...
  4. Howard A Rockman; Fiscal Year: 2016
    ..of G protein activation;Project 2 (Koch) will study novel aspects of the G protein-coupled receptor kinase-2(GRK2), and its important roles in the signaling and physiology of the heart;Project 3 (Stamler) will study a newparadigm ..
  5. The Regulation of Plasma Membrane Estrogen Receptor-a Levels by Endocytosis
    Reymundo Dominguez; Fiscal Year: 2012
    ..2) Estradiol treatment of primary hippocampal and cortical neurons (a) rapidly initiates GRK2 (G protein-coupled receptor kinase-2) activation, and (b) promotes the formation of ER[unreadable]/[unreadable]-..
  6. BARRY S KREUTZ; Fiscal Year: 2014
    ..2) We successfully applied similar purification strategy for Gq and determined the crystal structure of Gq-GRK2-Gbetagamma complex. Also, we discovered a novel RhoGEF, p63RhoGEF as a direct effector for Gq...
  7. Transgenic Targeting of Vascular G Protein Signaling
    Karsten Peppel; Fiscal Year: 2010
    ..For example, a large portion of GRK phosphorylation of either angiotensin II or vasopressin receptor is GRK2 mediated and leads to arrestin recruitment and internalization...
  8. G-Protein Coupled Receptor Kinase-2 on IgE Signaling in Mast Cells
    Hydar Ali; Fiscal Year: 2012
    ..Unexpectedly, we found that silencing GRK2 expression in human mast cells substantially inhibits Fc5RI-mediated degranulation...
  9. Walter J Koch; Fiscal Year: 2016
    Targeting GRK2 ([unreadable]ARK1) in Heart Failure ABSTRACT Heart Failure (HF) continues to grow in the country and is a burden to the health care enterprise...
  10. Exploring a Role for beta-Arrestins in Cardiac Injury and Repair
    Anna M Gumpert; Fiscal Year: 2013
    ..Walter J. Koch) laboratory has identified a key role for G protein- coupled receptor (GPCR) kinase-2 (GRK2) in the pathophysiology of injured and stressed myocardium...
  11. EMMANUEL MODESTO AWUMEY; Fiscal Year: 2014
    ..of Ca2+i within sensory nerves, coupled to G[unreadable]q, is desensitized by G protein receptor kinase 2 (GRK2)-mediated uncoupling of the receptor from G protein...
  12. Jianhang Jia; Fiscal Year: 2016
    ..gradient Hh activity;2) to investigate the molecular mechanisms by which G protein-coupled receptor kinase 2 (GRK2) is involved in Hh signaling;and 3) to determine the role of phosphatase in Smo dephosphorylation and inactivation...
  13. SATHYAMANGLA VENKATA PRASAD; Fiscal Year: 2016
    ..Receptor desensitization is initiated by the phosphorylation of agonist activated bARs by bAR kinase-1 (bARK1). b-arrestin binds to the phosphorylated receptor resulting in the loss of effector (adenylyl cyclase) signaling...
  14. RGS Protein Regulation of G Protein Coupled Receptors
    John R Hepler; Fiscal Year: 2010
    ..Aim 3: Determine the effects of RGS2 on GRK2 binding/phosphorylation and arrestin binding to receptors on their desensitization, internalization, and ..
  15. Nitric Oxide and the Cellular Pathogenesis of Portal Hypertension
    Don C Rockey; Fiscal Year: 2012
    ..New data indicate that GRK2 interacts with and affects Akt activity...
  16. MARK E VONZASTROW; Fiscal Year: 2016
    ..Preliminary studies using these models suggest a specific requirement for GRK2, a receptor kinase known to modulate opioid receptor endocytosis in cultured cell models, in mediating a sustained ..
  17. Gerald W Dorn; Fiscal Year: 2016
    ..Clinical and pre-clinical trials are already underway evaluating isoform-specific GRK2 and PKC[unreadable] inhibition in cardiac ischemia and heart failure;and 3...
  18. Targeting of B-AR/GBy signaling in the heart with small molecules
    Burns C Blaxall; Fiscal Year: 2013
    ..They recruit elevated levels of cytosolic G-protein coupled receptor kinase 2 (GRK2, bARK1) to agonist-stimulated b-ARs in HF, leading to the chronic b-AR desensitization and down-regulation that are ..
  19. Sally E Wenzel; Fiscal Year: 2014
    ..In Aim 3, we will determine whether the interaction of 15 HETE-PE with PEBP1 competitively inhibits the binding of GRK2 to PEBP1, leading to enhanced desensitization of 2[unreadable]AR in vitro and in vivo in human asthmatics...
  20. John J G Tesmer; Fiscal Year: 2016
    ..resolution crystal structures that represent all three GRK subfamilies, including that of GRK1 (rhodopsin kinase), GRK2 (2-adrenergic receptor kinase 1), and GRK6, as well as structures of GRK2 in complex with heterotrimeric G1q and ..
  21. Yue Xiong; Fiscal Year: 2016
    ..unreadable] subunit 2 (G[unreadable]2), associates with DDB1- CUL4A to target G protein-coupled receptor kinases (GRK2), for ubiquitylation...
  22. Therapeutic Small Molecule Modulators of G beta gama Signaling
    Val S Goodfellow; Fiscal Year: 2011
    ..assay will be used to prioritize compounds, followed by secondary assays for inhibition of PLC activation and GRK2 G binding inhibition...
  23. CD3 e functions in T cells
    NICOLAI VAN OERS; Fiscal Year: 2009
    ..sequence the basic rich stretch, and have determined that it can interact with a serine/threonine kinase termed GRK2, and can also interact with phospholipids...
  24. MECHANISMS OF G PROTEIN COUPLED RECEPTOR REGULATION
    LAWRENCE BARAK; Fiscal Year: 2002
    ..Assays based upon the ability to visualize the behavior of the beta2AR or the substance P receptor, GRK2, and beta-arrestin 1 and 2, utilizing their fluorescent chimeras, will be employed to follow receptor ..
  25. Regulation of Cardiac Adrenergic Function by S-nitrosylation
    JONATHAN STAMLER; Fiscal Year: 2009
    ..appear to be mediated, in significant part, by S-nitrosylation of the G protein- coupled receptor (GPCR) kinase, GRK2. Additional components of the ?-AR system are also regulated by S- nitrosylation, which suggests a broad functional ..
  26. Molecular basis of mechanotransduction in bone cells
    Jun You; Fiscal Year: 2013
    ..Our results suggest that G-protein coupled receptor kinase 2 (GRK2) is involved in the desensitization of P2Y activation in response to fluid flow...
  27. G Protein Coupled Receptor Regulatory Mechanisms in Arthritis
    TERESA KATHLEEN TARRANT; Fiscal Year: 2010
    ..Previous studies from the Patel laboratory have shown that deficiencies in GRK6 or GRK2 affect the migration of leukocyte subsets in vitro and in vivo...
  28. Derek C Molliver; Fiscal Year: 2016
    ..through Gi/o in hyperalgesia resulting from inflammatory injury, the regulation of P2Y signaling by GPCR kinases GRK2 and GRK3 during hyperalgesia, and will explore the hypothesis that these receptors are highly effective in ..
  29. Role of receptor trafficking in synaptic plasticity during morphine dependence
    Anuradha Madhavan; Fiscal Year: 2013
    ..endocytosis could be due to reduced expression or lack of recruitment of the G-protein coupled receptor kinase2 (GRK2)...
  30. Annemieke Kavelaars; Fiscal Year: 2015
    ..We recently discovered that G protein-coupled receptor kinase 2 (GRK2) is key to preventing transition to chronic hyperalgesia...
  31. Annemieke Kavelaars; Fiscal Year: 2016
    ..We recently made the exciting discovery that an intracellular protein known as G protein coupled receptor kinase 2 (GRK2) possesses anti-inflammatory properties and acts as a molecular switch that regulates transition from acute to ..
  32. Novel GPCR Kinase Interactions in Macrophages and Role in Arthritis
    Narayanan Parameswaran; Fiscal Year: 2009
    ..Role of GRK2 and 5 in TNF signaling represents a novel signaling paradigm and thus understanding the mechanisms by which these ..
  33. PHARMACOLOGIC PROMOTION OF WOUND HEALING
    Bruce Cronstein; Fiscal Year: 2007
    ..on adenosine A2A receptor mRNA, protein and function as well as adenosine A2A receptor desensitization mechanisms (GRK2 recruitment to the plasma membrane) will be tested both in vitro and in vivo (RAGE and A1 KO mice)...
  34. GRK2 - MEDIATED REGULATION OF MGLUR5 SIGNALING
    SCOTT SORENSEN; Fiscal Year: 2002
    ..The purpose of these studies is to determine the role that G-protein-coupled receptor kinase 2 (GRK2) plays in regulating the function of metabotropic glutamate receptor 5 (mGluR5)...
  35. MOLECULAR BASIS FOR PROTEIN/PHOSPHOLIPID INTERACTION
    Jon Lomasney; Fiscal Year: 2003
    ..A series of PLC delta1 chimeras containing PH domains from other molecules such as GRK2 will be constructed and characterized...
  36. Dopamine Receptor Trafficking in Parkinson's Disease
    Eugenia Gurevich; Fiscal Year: 2007
    ..To that end, lentivirus-mediated gene transfer of GRK2 or its inhibitor into the lesioned rat striatum will be used...
  37. ANTIPSYCHOTICS AND RECEPTOR DESENSITIZATION MACHINERY
    Eugenia Gurevich; Fiscal Year: 2002
    ..We expect that the information gained by examining the response of the key components of the receptor trafficking machinery to antipsychotics will be helpful for targeted design of drugs with improved clinical profile. ..
  38. RESPONSIVENESS OF GNRH RECEPTOR SIGNALING
    JIMMY NEILL; Fiscal Year: 2002
    ..The Specific Aims of the proposal are: Specific Aim 1: Determine the effects of GRK2, GRK3, beta arrestin 1 and 2 alone and in combination on GnRH-stimulated LH secretion using adenoviral-mediated ..
  39. G Protein-Mediated Signal Transduction in Brain
    Tohru Kozasa; Fiscal Year: 2004
    ..We will also investigate the mechanism of regulation of this pathway by receptor activation, RGS proteins, or by other G protein-mediated pathway. ..
  40. Chronic Ethanol Effects on CNS Opiate Receptors
    Linda Saland; Fiscal Year: 2003
    ..It will also be possible to study the functional changes that may occur in the receptors after withdrawal from consumption. A future potential may be then to target delta receptors for treating chronic alcoholism. ..
  41. Stem cell-based therapy in heart failure: aging effects
    Mohamed Gaballa; Fiscal Year: 2003
    ..abstract_text> ..
  42. RECEPTOR KINASE GENE THERAPY FOR NEOINTIMAL HYPERPLASIA
    Neil Freedman; Fiscal Year: 2002
    ..Over-expression of GRK2 can drastically reduce signaling through all of these receptors in transfected cell systems...
  43. IONIC CURRENTS AND AUTONOMIC REGULATION IN HEART FAILURE
    Atsuko Yatani; Fiscal Year: 2002
    ....
  44. PHOSPHOLIPASE C AND CARDIAC HYPERTROPHY
    GERALD DORN; Fiscal Year: 2005
    ..abstract_text> ..
  45. GENE TRANSFER TO ALTER TRANSPLANTED HEART FUNCTION
    Walter Koch; Fiscal Year: 2004
    ..Transgenic mice have been developed with altered BAR and G protein signaling, including mice in which BAR-kinase (BARK1) is overexpressed...
  46. G-PROTEIN COUPLED RECEPTOR KINASES IN OSTEOGENESIS
    Robert Spurney; Fiscal Year: 2004
    ..Understanding the biochemical mechanisms that regulate hone formation could lead to the development of novel strategies for treating a wide variety of bone disorders that cause osteoporosis. ..
  47. TARGETING G PROTEINS IN VASCULAR INTIMAL HYPERPLASIA
    Walter Koch; Fiscal Year: 2003
    ..abstract_text> ..
  48. SIGNALING PATHWAYS OF ARF GTPASES AND ARF GAPS
    Richard Premont; Fiscal Year: 2005
    ..abstract_text> ..
  49. THE FUNCTION OF NEUROTRANSMITTERS IN BONE BIOLOGY
    MATTHEW BLIZIOTES; Fiscal Year: 2009
    ..This research should contribute to new treatment and prevention regimens for osteoporosis and thus have a significant positive impact on the health care of the aging population. ..
  50. Inhibitory AT2 Receptor:Activation/Signaling Mechanisms
    Ying Hong Feng; Fiscal Year: 2005
    ..This proposal has the potential to open up novel avenues for therapy of hypertrophy and fibrosis. ..
  51. Aging, Atherosclerosis, and the Arterial Wall
    Neil Freedman; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  52. Gene Transfer and Myocardial Function
    Walter Koch; Fiscal Year: 2008
    ..receptor (betaAR) signaling in the hypertrophic and failing heart and found that the betaAR kinase (betaARK1 or GRK2) plays a critical role in the pathogenesis of HF...
  53. Regulation of Podocyte Function By Angiotensin II
    Robert Spurney; Fiscal Year: 2008
    ..abstract_text> ..
  54. Innovative Assays for Oncogenic Hedgehog Signaling
    Wei Chen; Fiscal Year: 2008
    ..In particular it should be possible to identify critical proteins modulating altered signaling pathways in pancreatic adenocarcinoma and design pharmacologic strategies to target them for therapeutic benefit. ..
  55. Dopamine Receptor Regulation by GRKs in Drug Abuse
    Richard Premont; Fiscal Year: 2008
    ..The results of these studies will define the role of GRK6 in setting the basal tone of dopamine signaling in the striatum. [unreadable] [unreadable] [unreadable]..
  56. TARGETING BETAARK1 IN HEART FAILURE
    Walter Koch; Fiscal Year: 2008
    ..the actions of G protein-coupled receptor kinases (GRKs), such as the (beta-adrenergic receptor kinase (betaARK1 or GRK2), are important in modulating normal and failing heart function...
  57. Calpains as Mediators of Cardiac Ischemic Injury
    Gerald W Dorn; Fiscal Year: 2010
    ..Collectively, these studies will apply state-of-the-art techniques for in vivo genetic manipulation, microphysiologic analysis, and biochemical assessment to achieve insight into the roles of myocardial calpains in health and disease. ..
  58. Mechanisms of Arterial Wall-Mediated Atherogenesis
    Neil Freedman; Fiscal Year: 2008
    ..In so doing, this project should build a foundation for identifying multiple arterial wall gene products that may serve as therapeutic targets for atherosclerosis. ..
  59. Novel Approaches for Burn Injury Cardiac Dysfunction
    Atsuko Yatani; Fiscal Year: 2009
    ..D. The name of the principal investigator/program director must be provided at the top of each printed page and each continuation page. RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page 1 Description, ..
  60. Desensitization of Vascular Receptor Tyrosine Kinases
    Neil Freedman; Fiscal Year: 2009
    ..in RPTKs important to cardiovascular physiology, using smooth muscle cells or fibroblasts derived from GRK2-, GRK5-, or GRK6-knockout mice, or from cognate GRK+/+ littermate control mice...
  61. Thrombin,Sepsis and Mechanisms of Inflammation
    Chinnaswamy Tiruppathi; Fiscal Year: 2010
    ..It is hoped that this work will lead to the development of new drug targeting acute lung injury associated with leaky lung microvessel and tissue edema formation. ..