PAK1

Summary

Gene Symbol: PAK1
Description: p21 (RAC1) activated kinase 1
Alias: PAKalpha, serine/threonine-protein kinase PAK 1, STE20 homolog, yeast, alpha-PAK, p21 protein (Cdc42/Rac)-activated kinase 1, p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast), p21/Cdc42/Rac1-activated kinase 1 (yeast Ste20-related), p65-PAK
Species: human

Top Publications

  1. pmc HIV-1 activates Cdc42 and induces membrane extensions in immature dendritic cells to facilitate cell-to-cell virus propagation
    Damjan S Nikolic
    Department of Dermatology and Venereology, Microbiology and Molecular Medicine, University Hospitals and Medical School of Geneva, Geneva, Switzerland
    Blood 118:4841-52. 2011
  2. ncbi SH3-Domain binding function of HIV-1 Nef is required for association with a PAK-related kinase
    A Manninen
    Institute of Medical Technology, University of Tampere, Tampere, FIN 33101, Finland
    Virology 250:273-82. 1998
  3. pmc p21-activated kinase 1 plays a critical role in cellular activation by Nef
    O T Fackler
    Howard Hughes Medical Institute, Departments of Medicine, Microbiology, and Immunology, San Francisco, California 94143 0703, USA
    Mol Cell Biol 20:2619-27. 2000
  4. pmc Increased Rac1 activity and Pak1 overexpression are associated with lymphovascular invasion and lymph node metastasis of upper urinary tract cancer
    Takao Kamai
    Department of Urology, Dokkyo Medical University, Mibu, Tochigi, Japan
    BMC Cancer 10:164. 2010
  5. doi P21-activated protein kinase 1 is overexpressed in gastric cancer and induces cancer metastasis
    Liang Hui Li
    Department of General Surgery, Zhongshan Hospital, Xiamen University, Xiamen 361004, PR China
    Oncol Rep 27:1435-42. 2012
  6. pmc Functional characterization of the human immunodeficiency virus type 1 Nef acidic domain
    Laura L Baugh
    Y9 206, Department of Internal Medicine, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    J Virol 82:9657-67. 2008
  7. doi P-21 activated kinase 1 knockdown inhibits β-catenin signalling and blocks colorectal cancer growth
    Hong He
    Department of Surgery, University of Melbourne, Austin Health, Melbourne, Victoria 3084, Australia
    Cancer Lett 317:65-71. 2012
  8. ncbi Increased p21-activated kinase-1 expression is associated with invasive potential in uveal melanoma
    Sandra Pavey
    Human Genetics Laboratory, Queensland Institute of Medical Research, Herston, Queensland, Australia
    Melanoma Res 16:285-96. 2006
  9. ncbi Correlations of P21-activated kinase 1 expression to clinicopathological features of gastric carcinoma and patients' prognosis
    Juan Xia Wang
    Department of Hepatopathy, The Second Hospital, Lanzhou University, Lanzhou, Gansu 730030, PR China
    Chin J Cancer 29:649-54. 2010
  10. ncbi Atypical mechanism of regulation of the Wrch-1 Rho family small GTPase
    Adam Shutes
    Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Curr Biol 14:2052-6. 2004

Research Grants

  1. Maria Diakonova; Fiscal Year: 2014
  2. NEUROFIBROMATOSIS TYPE 1 GENE REGULATES MYELOPOIESIS
    DAVID W CLAPP; Fiscal Year: 2012
  3. A novel therapy for HER2 positive hormone refractory breast cancer
    Anne W Hamburger; Fiscal Year: 2010
  4. Jun Li; Fiscal Year: 2016
  5. Human pathogenic bacterium induces actin phosphorylation to selectively regulate
    Hameeda Sultana; Fiscal Year: 2012
  6. Post-ischemic cardiac remodeling
    MICHELLE MONASKY; Fiscal Year: 2012
  7. CIB1 regulation of endothelial function
    Leslie V Parise; Fiscal Year: 2013
  8. Scott J Russo; Fiscal Year: 2016
  9. Gadiparthi N Rao; Fiscal Year: 2016
  10. Receptor Trafficking in Entry of Murine Leukemia Viruses
    Robert A Davey; Fiscal Year: 2011

Detail Information

Publications217 found, 100 shown here

  1. pmc HIV-1 activates Cdc42 and induces membrane extensions in immature dendritic cells to facilitate cell-to-cell virus propagation
    Damjan S Nikolic
    Department of Dermatology and Venereology, Microbiology and Molecular Medicine, University Hospitals and Medical School of Geneva, Geneva, Switzerland
    Blood 118:4841-52. 2011
    ..extensions are induced after engagement of DC-SIGN by HIV-1(env) via a cascade that involves Src kinases, Cdc42, Pak1, and Wasp...
  2. ncbi SH3-Domain binding function of HIV-1 Nef is required for association with a PAK-related kinase
    A Manninen
    Institute of Medical Technology, University of Tampere, Tampere, FIN 33101, Finland
    Virology 250:273-82. 1998
    ..Molecular modeling suggests that these residues are involved in formation of an adjacent binding surface for NAK or another critical component of the NAK/Nef complex...
  3. pmc p21-activated kinase 1 plays a critical role in cellular activation by Nef
    O T Fackler
    Howard Hughes Medical Institute, Departments of Medicine, Microbiology, and Immunology, San Francisco, California 94143 0703, USA
    Mol Cell Biol 20:2619-27. 2000
    ..In this study, we identified NAK as p21-activated kinase 1 (PAK1). PAK1 bound to Nef in vitro and in vivo...
  4. pmc Increased Rac1 activity and Pak1 overexpression are associated with lymphovascular invasion and lymph node metastasis of upper urinary tract cancer
    Takao Kamai
    Department of Urology, Dokkyo Medical University, Mibu, Tochigi, Japan
    BMC Cancer 10:164. 2010
    ....
  5. doi P21-activated protein kinase 1 is overexpressed in gastric cancer and induces cancer metastasis
    Liang Hui Li
    Department of General Surgery, Zhongshan Hospital, Xiamen University, Xiamen 361004, PR China
    Oncol Rep 27:1435-42. 2012
    P21-activated protein kinase (Pak1), a main downstream effector of small Rho GTPases, plays an important role in the regulation of cell morphogenesis, motility, mitosis and angiogenesis...
  6. pmc Functional characterization of the human immunodeficiency virus type 1 Nef acidic domain
    Laura L Baugh
    Y9 206, Department of Internal Medicine, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    J Virol 82:9657-67. 2008
    ..Our results are consistent with an alternative model in which (62)EEEE(65) plays a stabilizing role in the formation of a ternary complex between Nef, the MHC-I cytoplasmic domain, and AP-1...
  7. doi P-21 activated kinase 1 knockdown inhibits β-catenin signalling and blocks colorectal cancer growth
    Hong He
    Department of Surgery, University of Melbourne, Austin Health, Melbourne, Victoria 3084, Australia
    Cancer Lett 317:65-71. 2012
    The p21-activated kinase 1 (PAK1) plays important roles in cell growth, motility, and transformation...
  8. ncbi Increased p21-activated kinase-1 expression is associated with invasive potential in uveal melanoma
    Sandra Pavey
    Human Genetics Laboratory, Queensland Institute of Medical Research, Herston, Queensland, Australia
    Melanoma Res 16:285-96. 2006
    ..Of particular interest, expression of two members of the p21-activated kinase (PAK) family, PAK1 and PAK7, was elevated in the more invasive cultures...
  9. ncbi Correlations of P21-activated kinase 1 expression to clinicopathological features of gastric carcinoma and patients' prognosis
    Juan Xia Wang
    Department of Hepatopathy, The Second Hospital, Lanzhou University, Lanzhou, Gansu 730030, PR China
    Chin J Cancer 29:649-54. 2010
    Recent studies proved that P21-activated kinase 1 (PAK1) is highly expressed in many kinds of tumor and plays an important role in genesis, development, and metastasis of tumor...
  10. ncbi Atypical mechanism of regulation of the Wrch-1 Rho family small GTPase
    Adam Shutes
    Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Curr Biol 14:2052-6. 2004
    ..We propose that Grb2 overcomes N-terminal negative regulation to promote Wrch-1 effector interaction. Thus, Wrch-1 exhibits an atypical model of regulation not seen in other Rho family GTPases...
  11. pmc p21-Activated kinase 1 (Pak1) phosphorylates BAD directly at serine 111 in vitro and indirectly through Raf-1 at serine 112
    Diana Z Ye
    Department of Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 6:e27637. 2011
    ..One of the critical phosphorylation sites is the serine 112 (S112), which can be phosphorylated by several kinases including Pak1.
  12. ncbi Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics
    D C Edwards
    Department of Chemistry, University of California at San Diego, La Jolla 92093 0650, USA
    Nat Cell Biol 1:253-9. 1999
    ..Here we show that p21-activated kinase (Pak1) phosphorylates LIM-kinase at threonine residue 508 within LIM-kinase's activation loop, and increases LIM-kinase-..
  13. ncbi p21-activated kinase (PAK1) is phosphorylated and activated by 3-phosphoinositide-dependent kinase-1 (PDK1)
    C C King
    Departments of Immunology and Cell Biology, Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 275:41201-9. 2000
    ..we show that phosphorylated 3-phosphoinositide-dependent kinase 1 (PDK1) phosphorylates p21-activated kinase 1 (PAK1) in the presence of sphingosine...
  14. ncbi Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Rac1
    Maria Carla Parrini
    Laboratory of Molecular Medicine, Boston, MA 02115, USA
    Mol Cell 9:73-83. 2002
    b>Pak1, a serine/threonine kinase that regulates the actin cytoskeleton, is an effector of the Rho family GTPases Cdc42 and Rac1. The crystal structure of Pak1 revealed an autoinhibited dimer that must dissociate upon GTPase binding...
  15. ncbi Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop
    K Ohashi
    Biological Institute, Graduate School of Science, Tohoku University, Sendai 980 8578, Japan
    J Biol Chem 275:3577-82. 2000
    ..Together with the recent finding that PAK1, a downstream effector of Rac, also activates LIMK1 by phosphorylation at Thr-508, these results suggest that ..
  16. pmc Tumor necrosis factor-alpha induced expression of matrix metalloproteinase-9 through p21-activated kinase-1
    Ling Zhou
    Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
    BMC Immunol 10:15. 2009
    ..In this study we investigated mechanism of cytokine induced MMP-9 with particular emphasis on the role of p21-activated-kinase-1 (PAK1) and the down stream signaling.
  17. pmc Phosphorylation of Raf-1 serine 338-serine 339 is an essential regulatory event for Ras-dependent activation and biological signaling
    B Diaz
    Department of Medicine, Walther Oncology Center, Indiana University School of Medicine, Indianapolis 46202, USA
    Mol Cell Biol 17:4509-16. 1997
    ....
  18. ncbi Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch
    M Lei
    Laboratory of Molecular Medicine, Children s Hospital, Boston, Massachusetts 02115, USA
    Cell 102:387-97. 2000
    ..crystal structure of a complex between the N-terminal autoregulatory fragment and the C-terminal kinase domain of PAK1 shows that GTPase binding will trigger a series of conformational changes, beginning with disruption of a PAK1 ..
  19. doi Reciprocal regulation of Rac1 and PAK-1 by HIF-1alpha: a positive-feedback loop promoting pulmonary vascular remodeling
    Isabel Diebold
    Department of Pediatric Cardiology, Technical University Munich, Munich, Germany
    Antioxid Redox Signal 13:399-412. 2010
    ....
  20. pmc p21-Activated kinase-1 promotes aggressive phenotype, cell proliferation, and invasion in gestational trophoblastic disease
    Michelle K Y Siu
    Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, China
    Am J Pathol 176:3015-22. 2010
    ..p21-Activated kinases (PAKs) promote malignant tumor progression. Therefore, this study investigated PAK1, PAK2, and p-PAK2 Ser(20) in the pathogenesis of GTD...
  21. doi Up-regulation of p21-activated kinase 1 by in vitro treatment with interleukin 1-beta and its increased expression in ovarian endometriotic cysts
    Mi Young Lee
    Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
    Fertil Steril 96:508-11. 2011
    We evaluated whether the proinflammatory cytokines can regulate p21-activated kinase (Pak1) expression in endometrial cells as well as whether its expression is increased in endometriotic cysts...
  22. pmc p21-Activated kinase 1 is required for efficient tumor formation and progression in a Ras-mediated skin cancer model
    Hoi Yee Chow
    Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Cancer Res 72:5966-75. 2012
    ..As p21-activated kinase 1 (Pak1) has been shown to regulate both these signaling pathways and is itself upregulated in many human cancers, we ..
  23. pmc p21-activated kinase-1 signaling regulates transcription of tissue factor and tissue factor pathway inhibitor
    Beatriz Sánchez-Solana
    Department of Biochemistry and Molecular Biology, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA
    J Biol Chem 287:39291-302. 2012
    ..study aimed at identifying differentially regulated genes between wild-type (WT) and p21-activated kinase 1-null (PAK1-KO) mouse embryonic fibroblasts (MEFs), we found TF and TFPI are differentially expressed in the PAK1-KO MEFs in ..
  24. ncbi Phorbol ester-induced migration of HepG2 cells is accompanied by intensive stress fibre formation, enhanced integrin expression and transient down-regulation of p21-activated kinase 1
    Annamária Gujdár
    Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University of Medicine, PO Box 260, 1444 Budapest, Hungary
    Cell Signal 15:307-18. 2003
    ..Protein kinase C stimulated the activation of p21-activated kinase (PAK), as well. However, it also stimulated the selective and transient down-regulation of PAK1, which coincided with the formation of stress fibres.
  25. ncbi Phosphorylation of Raf-1 by p21-activated kinase 1 and Src regulates Raf-1 autoinhibition
    Nancy H Tran
    Department of Integrative Biology and Pharmacology, University of Texas Houston Health Science Center, Houston, Texas 77030, USA
    J Biol Chem 278:11221-6. 2003
    ..We also show that phosphorylation of Raf-1 on serine 338 by PAK1 and tyrosines 340 and 341 by Src relieves autoinhibition and that this occurs through a specific decrease in the ..
  26. ncbi Association between Pak1 expression and subcellular localization and tamoxifen resistance in breast cancer patients
    Caroline Holm
    Division of Pathology, Department of Laboratory Medicine, Lund University, Malmo, Sweden
    J Natl Cancer Inst 98:671-80. 2006
    p21-activated kinase 1 (Pak1) phosphorylates many proteins in both normal and transformed cells...
  27. ncbi Amplification of CCND1 and PAK1 as predictors of recurrence and tamoxifen resistance in postmenopausal breast cancer
    J Bostner
    Department of Biomedicine and Surgery, Division of Oncology, Faculty of Health Sciences, Linkoping University, Linkoping, Sweden
    Oncogene 26:6997-7005. 2007
    ..Situated in this region are the cyclin D1 gene (CCND1) and the p-21-activated kinase 1 (PAK1) gene...
  28. ncbi p21-activated kinase 1 phosphorylates and regulates 14-3-3 binding to GEF-H1, a microtubule-localized Rho exchange factor
    Frank T Zenke
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 279:18392-400. 2004
    ..We identify GEF-H1 as a binding target and substrate for p21-activated kinase 1 (PAK1), an effector of Rac and Cdc42 GTPases, using an affinity-based screen and localize a PAK1 phosphorylation site to ..
  29. ncbi NF-kappaB- and C/EBPbeta-driven interleukin-1beta gene expression and PAK1-mediated caspase-1 activation play essential roles in interleukin-1beta release from Helicobacter pylori lipopolysaccharide-stimulated macrophages
    Chaitali Basak
    Department of Chemistry, Bose Institute, 93 1 Acharya Prafulla Chandra Road, Kolkata 700009, India
    J Biol Chem 280:4279-88. 2005
    ..Most important, we observed a role of Rac1/PAK1 signaling in activation of caspase-1, which is necessary for maturation of pro-IL-1beta. H...
  30. pmc ERK activation of p21 activated kinase-1 (Pak1) is critical for medulloblastoma cell migration
    Liangping Yuan
    Aflac Center for Cancer and Blood Disorders, Emory University School of Medicine, Atlanta, GA 30322, USA
    Clin Exp Metastasis 27:481-91. 2010
    ..In this study, we investigated whether ERK regulates Rac1/Pak1 signaling and is critically linked to MB cell migration...
  31. ncbi Human p21-activated kinase (Pak1) regulates actin organization in mammalian cells
    M A Sells
    Fox Chase Cancer Centre, 7701 Burholme Avenue, Philadelphia, Pennsylvania 19111, USA
    Curr Biol 7:202-10. 1997
    ..This kinase is therefore a candidate effector for the changes in cell shape induced by growth factors...
  32. ncbi The protein kinase Pak3 positively regulates Raf-1 activity through phosphorylation of serine 338
    A J King
    Department of Medicine, Indiana University School of Medicine, The Walther Oncology Center, Indianapolis 46202, USA
    Nature 396:180-3. 1998
    ..As guanine-nucleotide-exchange activity on Rac can be stimulated by a Ras-dependent phosphatidylinositol-3-OH kinase, a mechanism could exist through which one Ras effector pathway can be influenced by another...
  33. ncbi PAK1 primes MEK1 for phosphorylation by Raf-1 kinase during cross-cascade activation of the ERK pathway
    Lucy C Coles
    School of Biomedical Sciences, University of Nottingham Medical School, Queen s Medical Centre, Nottingham NG7 2UH, UK
    Oncogene 21:2236-44. 2002
    ..Here we show that both Raf-1 and MEK1 are phosphorylated by PAK1 and that mutations at PAK1 phosphorylation sites in either protein prevent cross-cascade activation...
  34. pmc p21-activated kinase 1 interacts with and phosphorylates histone H3 in breast cancer cells
    Feng Li
    The University of Texas MD Anderson Cancer Center, Houston 77030, USA
    EMBO Rep 3:767-73. 2002
    Stimulation of p21-activated kinase-1 (Pak1) signaling promotes motility, invasiveness, anchorage-independent growth and abnormal mitotic assembly in human breast cancer cells...
  35. ncbi Cdc42/Rac1-dependent activation of the p21-activated kinase (PAK) regulates human platelet lamellipodia spreading: implication of the cortical-actin binding protein cortactin
    Catherine Vidal
    Departement d Hematologie, Institut Cochin, Centre National de la Recherche Scientifique CNRS, Universite Rene Descartes, Laboratoire Central d Hématologie, Hopital Cochin, AP HP and E9907 INSERM, Faculte Xavier Bichat, Paris, France
    Blood 100:4462-9. 2002
    ..These results suggest that Cdc42/Rac1-dependent activation of PAK may trigger early platelet shape change, at least in part through the regulation of cortactin binding to PAK...
  36. ncbi Phosphorylation of RhoGDI by Pak1 mediates dissociation of Rac GTPase
    Celine DerMardirossian
    Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Mol Cell 15:117-27. 2004
    ..We identified a RhoGDI kinase from bovine brain as p21-activated kinase (Pak). Pak1 binds and phosphorylates RhoGDI both in vitro and in vivo at Ser101 and Ser174...
  37. pmc Determinants in HIV-1 Nef for enhancement of virus replication and depletion of CD4+ T lymphocytes in human lymphoid tissue ex vivo
    Stefanie Homann
    Department of Virology, University of Heidelberg, Germany
    Retrovirology 6:6. 2009
    ....
  38. pmc Pak protein kinases and their role in cancer
    Bettina Dummler
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cancer Metastasis Rev 28:51-63. 2009
    ..Pak-targeted therapeutics may efficiently inhibit certain types of tumors and efforts to identify selective Pak-inhibitors are underway...
  39. pmc Identification of novel in vivo phosphorylation sites of the human proapoptotic protein BAD: pore-forming activity of BAD is regulated by phosphorylation
    Lisa Polzien
    Institute for Medical Radiation and Cell Research, University of Wuerzburg, 97078 Wuerzburg, Germany
    J Biol Chem 284:28004-20. 2009
    ..This pore-forming capacity was dependent on phosphorylation status and interaction with 14-3-3 proteins. Collectively, our findings provide new insights into the regulation of BAD function by phosphorylation...
  40. doi Estrogen receptor-alpha phosphorylation at serine 305, nuclear p21-activated kinase 1 expression, and response to tamoxifen in postmenopausal breast cancer
    Josefine Bostner
    Division of Surgery and Clinical Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoping University, Linkoping, Sweden
    Clin Cancer Res 16:1624-33. 2010
    In vitro, p21-activated kinase 1 (Pak1) phosphorylates the serine 305 residue of the estrogen receptor alpha (ERalpha) and influences the response of breast cancer cells to tamoxifen...
  41. pmc Human immunodeficiency virus type 1 Nef associates with a member of the p21-activated kinase family
    M F Nunn
    Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, Maryland 20892, USA
    J Virol 70:6157-61. 1996
    ..PAKs initiate kinase cascades in response to environmental stimuli, and their identification as a target of Nef implicates these signaling molecules in HIV pathogenesis and provides a novel target for clinical intervention...
  42. ncbi p21-activated kinase links Rac/Cdc42 signaling to merlin
    Guang Hui Xiao
    Human Genetics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Biol Chem 277:883-6. 2002
    ..These biochemical investigations provide insights into the regulation of merlin function and establish a framework for elucidating tumorigenic mechanisms involved in neoplasms associated with merlin inactivation...
  43. ncbi HIV-1 Nef mimics an integrin receptor signal that recruits the polycomb group protein Eed to the plasma membrane
    Vanessa Witte
    Department of Dermatology, University of Erlangen Nurnberg, 91052 Erlangen, Germany
    Mol Cell 13:179-90. 2004
    ..Our results suggest a link between membrane-associated activation processes and transcriptional derepression and demonstrate how HIV exploits this mechanism...
  44. pmc Activation of the PAK-related kinase by human immunodeficiency virus type 1 Nef in primary human peripheral blood lymphocytes and macrophages leads to phosphorylation of a PIX-p95 complex
    A Brown
    Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016, USA
    J Virol 73:9899-907. 1999
    ..These results identify the PIX-p95 complex as a novel effector of Nef in primary cells and suggest that the regulation of the PAK signaling pathway may differ in T cells and macrophages...
  45. pmc Serine and tyrosine phosphorylations cooperate in Raf-1, but not B-Raf activation
    C S Mason
    CRC Centre for Cell and Molecular Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB
    EMBO J 18:2137-48. 1999
    ..Thus, there are considerable differences between the activation of the Raf proteins; Ras-GTP mediates two phosphorylation events required for Raf-1 activation but does not regulate such events for B-Raf...
  46. ncbi Phosphorylation of Pak1 by the p35/Cdk5 kinase affects neuronal morphology
    T Rashid
    Molecular and Developmental Neurobiology Medical Research Council Centre, New Hunt s House, King s College London, London, SE1 1UL, United Kingdom
    J Biol Chem 276:49043-52. 2001
    The small GTPase Rac and its effectors, the Pak1 and p35/Cdk5 kinases, have been assigned important roles in regulating cytoskeletal dynamics in neurons...
  47. pmc P21-activated kinase-1 phosphorylates and transactivates estrogen receptor-alpha and promotes hyperplasia in mammary epithelium
    Rui An Wang
    Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030 4009, USA
    EMBO J 21:5437-47. 2002
    Stimulation of p21-activated kinase-1 (Pak1) induces cytoskeleton reorganization and signaling pathways in mammary cancer cells...
  48. ncbi p21-activated kinase 1 (PAK1) interacts with the Grb2 adapter protein to couple to growth factor signaling
    Lorena A Puto
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 278:9388-93. 2003
    ..p21-activated kinase 1 (PAK1) is an effector of Rac/Cdc42 GTPases that has been implicated in the regulation of cytoskeletal dynamics, ..
  49. pmc Human immunodeficiency virus type 1 Tat regulates endothelial cell actin cytoskeletal dynamics through PAK1 activation and oxidant production
    Ru Feng Wu
    The University of Texas Southwestern Medical Center and the Dallas Veterans Administration Medical Center, Dallas, Texas 75216, USA
    J Virol 78:779-89. 2004
    ..Because active mutants of p21-activated kinase 1 (PAK1) induce identical changes in actin dynamics, we hypothesized that Tat exerts its cytoskeletal effects through PAK1...
  50. ncbi Regulation of phosphoglucomutase 1 phosphorylation and activity by a signaling kinase
    Anupama Gururaj
    Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Oncogene 23:8118-27. 2004
    ..of cross-talk between cell signaling and metabolic pathways, whereby the signaling kinase p21-activated kinase 1 (Pak1) binds to, phosphorylates and enhances the enzymatic activity of phosphoglucomutase 1 (PGM), an important ..
  51. ncbi Nuclear localization and chromatin targets of p21-activated kinase 1
    Rajesh R Singh
    Department of Molecular and Cellular Oncology, University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 280:18130-7. 2005
    b>Pak1 (p21-activated kinase 1), a conserved, mammalian signaling kinase, is a downstream effector of small GTPases Rac1 and Cdc42 and of growth factor signaling...
  52. pmc p21-activated kinase 1 regulates microtubule dynamics by phosphorylating tubulin cofactor B
    Ratna K Vadlamudi
    Box 108, University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
    Mol Cell Biol 25:3726-36. 2005
    p21-activated kinase 1 (Pak1) induces cytoskeleton reorganization in part by regulating microtubule dynamics through an elusive mechanism...
  53. pmc P21-activated kinase 1: convergence point in PDGF- and LPA-stimulated collagen matrix contraction by human fibroblasts
    Sangmyung Rhee
    Department of Cell Biology, University of Texas Southwestern Medical School, Dallas, TX 75390, USA
    J Cell Biol 172:423-32. 2006
    ..show that the PDGF and LPA signaling pathways required for matrix contraction converge on p21-activated kinase 1 (PAK1) and its downstream effector cofilin1 and that contraction depends on cellular ruffling activity, rather than on ..
  54. ncbi A Phosphatidylinositol 3-kinase-regulated Akt-independent signaling promotes cigarette smoke-induced FRA-1 expression
    Qin Zhang
    Department of Environmental Health Sciences, Bloomberg School of Public Health and Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205, USA
    J Biol Chem 281:10174-81. 2006
    ....
  55. ncbi Phosphorylation-dependent regulation of stability and transforming potential of ETS transcriptional factor ESE-1 by p21-activated kinase 1
    Bramanandam Manavathi
    Department of Molecular and Cellular Oncology, University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 282:19820-30. 2007
    ..Here we found that a signaling kinase, p21-activated kinase-1 (Pak1), interacts with and phosphorylates ESE-1...
  56. ncbi p21-Activated kinase-1 and its role in integrated regulation of cardiac contractility
    Katherine A Sheehan
    Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, 835 S Wolcott Ave, Chicago, IL 60612 7342, USA
    Am J Physiol Regul Integr Comp Physiol 293:R963-73. 2007
    ..cardiac contractility involving variations in the activity of the multifunctional enzyme, p21-activated kinase 1 (Pak1), a member of a family of proteins in the small G protein-signaling pathway that is activated by Cdc42 and Rac1...
  57. ncbi alpha6beta4 integrin activates Rac-dependent p21-activated kinase 1 to drive NF-kappaB-dependent resistance to apoptosis in 3D mammary acini
    Julie C Friedland
    Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Cell Sci 120:3700-12. 2007
    ..We report that elevated (alpha6)beta4 integrin-dependent Rac-Pak1 signaling supports resistance to apoptosis in mammary acini by permitting stress-dependent activation of the p65 ..
  58. ncbi p21-activated kinase 1 promotes soluble mutant huntingtin self-interaction and enhances toxicity
    Shouqing Luo
    Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome MRC Building, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2XY, UK
    Hum Mol Genet 17:895-905. 2008
    ..Here we report that p21-activated kinase 1 (Pak1) binds to htt in vivo and in vitro...
  59. pmc p21-Activated kinase 1 coordinates aberrant cell survival and pericellular proteolysis in a three-dimensional culture model for premalignant progression of human breast cancer
    Quanwen Li
    Department of Pharmacology and Barbara Ann Karmanos Cancer Institute, Wayne State University, 540 East Canfield Ave, Detroit, MI 48201, USA
    Neoplasia 10:314-29. 2008
    Overexpression of p21-activated kinase 1 (PAK1) occurs during the progression of human breast cancer. We have investigated the role of PAK1 in the premalignant progression of the MCF10 series of human breast epithelial cell lines...
  60. pmc Expression of active p21-activated kinase-1 induces Ca2+ flux modification with altered regulatory protein phosphorylation in cardiac myocytes
    Katherine A Sheehan
    Department of Physiology and Biophysics, Department of Medicine, Center for Cardiovascular Research, University of Illinois at Chicago, 835 S Wolcott Ave, Chicago, IL 60612 7342, USA
    Am J Physiol Cell Physiol 296:C47-58. 2009
    p21-Activated kinase-1 (Pak1) is a serine-threonine kinase that associates with and activates protein phosphatase 2A in adult ventricular myocytes and, thereby, induces increased Ca2+ sensitivity of skinned-fiber tension development ..
  61. doi The rho guanosine 5'-triphosphatase, cell division cycle 42, is required for insulin-induced actin remodeling and glucagon-like peptide-1 secretion in the intestinal endocrine L cell
    Gareth E Lim
    Department of Physiology, University of Toronto, Toronto, Ontario, Canada
    Endocrinology 150:5249-61. 2009
    ..After insulin treatment, Cdc42-dependent p21-activated kinase-1 (PAK1) activation was also detected, and transfection of small-interfering RNA against Cdc42 or of dominant-negative ..
  62. pmc A novel serine kinase activated by rac1/CDC42Hs-dependent autophosphorylation is related to PAK65 and STE20
    G A Martin
    Onyx Pharmaceuticals, Richmond, CA 94806, USA
    EMBO J 14:1970-8. 1995
    ..These data are consistent with a model in which hPAK65 functions as an effector molecule for rac1 and CDC42Hs...
  63. ncbi A brain serine/threonine protein kinase activated by Cdc42 and Rac1
    E Manser
    Institute of Molecular and Cell Biology, National University of Singapore, Kent Ridge
    Nature 367:40-6. 1994
    ..This bimolecular interaction provides a model for studying p21 regulation of mammalian phosphorylation signalling pathways...
  64. ncbi Human Ste20 homologue hPAK1 links GTPases to the JNK MAP kinase pathway
    J L Brown
    Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
    Curr Biol 6:598-605. 1996
    ..Clues to PAK function have come from studies of Ste20, which controls the activity of the yeast mating mitogen-activated protein (MAP) kinase cascade, in response to a heterotrimeric G protein and Cdc42...
  65. ncbi Interaction of the Nck adapter protein with p21-activated kinase (PAK1)
    G M Bokoch
    Department of Immunology and Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 271:25746-9. 1996
    ..We describe here a specific interaction of the Nck adapter molecule with PAK1 both in vitro and in vivo...
  66. ncbi HIV-1 Nef association with cellular serine kinase correlates with enhanced virion infectivity and efficient proviral DNA synthesis
    M Wiskerchen
    Aaron Diamond AIDS Research Center, New York, New York 10016, USA
    Virology 224:292-301. 1996
    ....
  67. ncbi Activation of PAK by HIV and SIV Nef: importance for AIDS in rhesus macaques
    E T Sawai
    Department of Medical Pathology, University of California, Davis 95616, USA
    Curr Biol 6:1519-27. 1996
    ..In tissue culture cells expressing Nef, this viral protein interacts with a cellular serine kinase, designated Nef-associated kinase...
  68. pmc Expression of constitutively active alpha-PAK reveals effects of the kinase on actin and focal complexes
    E Manser
    Glaxo IMCB Group, Institute of Molecular and Cell Biology, National University of Singapore, Kent Ridge
    Mol Cell Biol 17:1129-43. 1997
    ..These data support our previous suggestions of a role for PAK downstream of both Cdc42 and Rac1 and indicate that PAK functions include the dissolution of stress fibers and reorganization of focal complexes...
  69. pmc Localization of p21-activated kinase 1 (PAK1) to pinocytic vesicles and cortical actin structures in stimulated cells
    S Dharmawardhane
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Cell Biol 138:1265-78. 1997
    ..We have examined the subcellular localization of endogenous PAK1 in fibroblast cell lines using specific PAK1 antibodies...
  70. pmc Cross-cascade activation of ERKs and ternary complex factors by Rho family proteins
    J A Frost
    U T Southwestern Medical Center, Department of Pharmacology, Dallas 75235 9041, USA
    EMBO J 16:6426-38. 1997
    ..Rho family proteins utilize PAKs for this effect, as expression of an active PAK1 mutant can substitute for Rho family small G proteins, and expression of an interfering PAK1 mutant blocks Rho-type ..
  71. pmc A conserved negative regulatory region in alphaPAK: inhibition of PAK kinases reveals their morphological roles downstream of Cdc42 and Rac1
    Z S Zhao
    Glaxo IMCB Group, Institute of Molecular and Cell Biology, Singapore, Singapore
    Mol Cell Biol 18:2153-63. 1998
    ..These results, coupled with previous observations with constitutively active PAK, demonstrate that these kinases play an important role downstream of Cdc42 and Rac1 in cytoskeletal reorganization...
  72. ncbi Detailed map of a region commonly amplified at 11q13-->q14 in human breast carcinoma
    S Bekri
    Instabilité et Altérations des Génomes, UNSA CNRS UMR 6549, Nice, France
    Cytogenet Cell Genet 79:125-31. 1997
    ..Four new genes were placed on the regional map, namely CBP2, CLNS1A, UVRAG, and PAK1. We have narrowed the core of the 11q13-->q14 amplicon to a 350-kb area encompassing D11S533, mostly on its ..
  73. ncbi PAK kinases are directly coupled to the PIX family of nucleotide exchange factors
    E Manser
    Glaxo IMCB Group, Institute of Molecular and Cell Biology, Singapore
    Mol Cell 1:183-92. 1998
    ..PIX can induce membrane ruffling, with an associated activation of Rac1. Our results suggest a role for PIX in Cdc42-to-Rac1 signaling, involving the PIX/PAK complex...
  74. ncbi Differential effects of PAK1-activating mutations reveal activity-dependent and -independent effects on cytoskeletal regulation
    J A Frost
    University of Texas Southwestern Medical Center, Dallas, Texas 75235 9041, USA
    J Biol Chem 273:28191-8. 1998
    ..Different forms of activated PAK1 have been reported to either promote membrane ruffling and focal adhesion assembly or cause focal adhesion ..
  75. ncbi Multisite autophosphorylation of p21-activated protein kinase gamma-PAK as a function of activation
    A Gatti
    Department of Biochemistry, University of California, Riverside, California 92521, USA
    J Biol Chem 274:8022-8. 1999
    ..Further, the phosphorylation of Ser-141, Ser-165, and Thr-402 was found to correlate with gamma-PAK activation...
  76. ncbi Inhibition of myosin light chain kinase by p21-activated kinase
    L C Sanders
    Departments of Immunology and Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Science 283:2083-5. 1999
    ..p21-activated kinase 1 (PAK1) phosphorylates MLCK, resulting in decreased MLCK activity...
  77. pmc p21-activated kinase 1 (Pak1) regulates cell motility in mammalian fibroblasts
    M A Sells
    Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Cell Biol 145:837-49. 1999
    The p21 (Cdc42/Rac) activated kinase Pak1 regulates cell morphology and polarity in most, if not all, eukaryotic cells...
  78. pmc Paxillin LD4 motif binds PAK and PIX through a novel 95-kD ankyrin repeat, ARF-GAP protein: A role in cytoskeletal remodeling
    C E Turner
    Department of Anatomy and Cell Biology, State University of New York, Health Science Center, Syracuse, New York 13210, USA
    J Cell Biol 145:851-63. 1999
    ..These data implicate paxillin as a mediator of p21 GTPase-regulated actin cytoskeletal reorganization through the recruitment to nascent focal adhesion structures of an active PAK/PIX complex potentially via interactions with p95PKL...
  79. ncbi Identification of a central phosphorylation site in p21-activated kinase regulating autoinhibition and kinase activity
    F T Zenke
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 274:32565-73. 1999
    ..We present biochemical evidence that an autoinhibitory domain (ID) contained within amino acid residues 67-150 of Pak1 interacts with the carboxyl-terminal kinase domain and that this interaction is regulated in a GTPase-dependent ..
  80. pmc p21-activated kinase 1 phosphorylates the death agonist bad and protects cells from apoptosis
    A Schurmann
    Institut fur Pharmakologie und Toxikologie, Medizinische Fakulät, Rheinisch Westfälische Technische Hochschule Aachen, D52057 Aachen, Germany
    Mol Cell Biol 20:453-61. 2000
    ..p21-activated kinase 1 (PAK1) is activated by IL-3 in FL5...
  81. ncbi Structure of Cdc42 bound to the GTPase binding domain of PAK
    A Morreale
    Cambridge Centre for Molecular Recognition, Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK
    Nat Struct Biol 7:384-8. 2000
    ..The structure, together with mutagenesis data, suggests reasons for the specificity of these interactions and provides insight into the mechanism of PAK activation...
  82. ncbi Localized Rac activation dynamics visualized in living cells
    V S Kraynov
    Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Science 290:333-7. 2000
    ..FLAIR exemplifies a generally applicable approach for examining spatio-temporal control of protein activity...
  83. ncbi HIV-1 Nef associated PAK and PI3-kinases stimulate Akt-independent Bad-phosphorylation to induce anti-apoptotic signals
    D Wolf
    Department of Dermatology Erlangen, University of Erlangen Nurnberg, Erlangen, Germany
    Nat Med 7:1217-24. 2001
    ..Nef anti-apoptotic effects are likely a crucial mechanism for viral replication in the host and thus in AIDS pathogenesis...
  84. ncbi Interaction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1
    Mengwei Zang
    Diabetes and Metabolism Research Unit, Endocrinology Section, Evans Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    J Biol Chem 277:4395-405. 2002
    ..Previous studies have shown that Pak1/2 is implicated in both Ras-dependent and -independent activation of Raf-1 by phosphorylating Raf Ser(338)...
  85. ncbi p21-activated kinases: three more join the Pak
    Zahara M Jaffer
    Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA
    Int J Biochem Cell Biol 34:713-7. 2002
    ..The Group I Paks (Pak1, Pak2, Pak3) have been studied in greater detail and shown to be involved in the regulation of cellular processes ..
  86. ncbi Filamin is essential in actin cytoskeletal assembly mediated by p21-activated kinase 1
    Ratna K Vadlamudi
    Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Nat Cell Biol 4:681-90. 2002
    The serine/threonine kinase p21-activated kinase 1 (Pak1) controls the actin cytoskeletal and ruffle formation through mechanisms that are independent of GTPase activity...
  87. ncbi The C-terminal kinase domain of the p34cdc2-related PITSLRE protein kinase (p110C) associates with p21-activated kinase 1 and inhibits its activity during anoikis
    She Chen
    Department of Biochemistry, Shanghai Medical Center, Fudan University formerly the Shanghai Medical University, People s Republic of China
    J Biol Chem 278:20029-36. 2003
    ..used the yeast two-hybrid system to screen a human fetal liver cDNA library and identified p21-activated kinase 1 (PAK1) as an interacting partner of p110C...
  88. ncbi HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication
    Alison L Greenway
    Macfarlane Burnet Institute for Medical Research and Public Health, Cnr Commercial and Punt Roads, Melbourne, Victoria 3004, Australia
    J Biosci 28:323-35. 2003
    ....
  89. pmc Pak1 and PIX regulate contact inhibition during epithelial wound healing
    Mirjam M P Zegers
    Department of Anatomy and Biochemistry and Biophysics, University of California San Francisco, Box 2140, 600 16th Street, San Francisco, CA 94143, USA
    EMBO J 22:4155-65. 2003
    ..we show that epithelial cells expressing constitutively active or kinase-dead mutants of the Rac/Cdc42 effector Pak1 fail to undergo growth arrest upon wound closure...
  90. pmc Combined array comparative genomic hybridization and tissue microarray analysis suggest PAK1 at 11q13.5-q14 as a critical oncogene target in ovarian carcinoma
    Peter Schraml
    Institute of Pathology, University Hospital, University of Basel, Schonbeinstrasse 40, 4031 Basel, Switzerland
    Am J Pathol 163:985-92. 2003
    ..DNA copy number gains were most frequently observed for PIK3CA on 3q (66%), PAK1 on 11q (59%), KRAS2 on 12p (55%), and STK15 on 20q (55%)...
  91. ncbi p21-activated kinase-1 signaling mediates cyclin D1 expression in mammary epithelial and cancer cells
    Seetharaman Balasenthil
    Department of Molecular and Cellular Oncology, University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 279:1422-8. 2004
    p21-activated kinase 1 (Pak1) has been shown recently to induce hyperplasia in the mammary epithelium, a phenotype also manifested by overexpression of cyclin D1, a known indicator of the proliferative stage...
  92. ncbi Merlin, the product of the Nf2 tumor suppressor gene, is an inhibitor of the p21-activated kinase, Pak1
    Joseph L Kissil
    Department of Biology and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Mol Cell 12:841-9. 2003
    ..We describe a novel interaction between merlin and p21-activated kinase 1 (Pak1), which is dynamic and facilitated upon increased cellular confluence...
  93. pmc p41-Arc subunit of human Arp2/3 complex is a p21-activated kinase-1-interacting substrate
    Ratna K Vadlamudi
    Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA
    EMBO Rep 5:154-60. 2004
    ..Here we show that p41-Arc interacts with p21-activated kinase 1 (Pak1) both in vitro and in vivo...
  94. ncbi Phosphoinositide-dependent kinase 1 and p21-activated protein kinase mediate reactive oxygen species-dependent regulation of platelet-derived growth factor-induced smooth muscle cell migration
    David S Weber
    Department of Medicine, Division of Cardiology, Emory University, Atlanta, GA 30322, USA
    Circ Res 94:1219-26. 2004
    ..kinase-1 [PDK1] site) was attenuated by ROS inhibition, and infection of VSMCs with dominant-negative PAK1 adenovirus attenuated migration...
  95. ncbi Pak-1 expression increases with progression of colorectal carcinomas to metastasis
    Julia H Carter
    Wood Hudson Cancer Research Laboratory, Newport, Kentucky 41071, USA
    Clin Cancer Res 10:3448-56. 2004
    ..Because Pak-1 plays a central role in regulating cell motility and invasiveness, we sought to determine whether Pak-1 may be involved in the malignant progression of colorectal carcinoma...
  96. ncbi Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes
    Ratna K Vadlamudi
    Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Cancer Cell 5:575-85. 2004
    We identified dynein light chain 1 (DLC1) as a physiologic substrate of p21-activated kinase 1 (Pak1). Pak1-DLC1 interaction plays an essential role in cell survival, which depends on Pak1's phosphorylation of DLC1 on Ser88...
  97. ncbi Pak1 phosphorylation of snail, a master regulator of epithelial-to-mesenchyme transition, modulates snail's subcellular localization and functions
    Zhibo Yang
    Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Cancer Res 65:3179-84. 2005
    ..Since the invasiveness of breast cancer cells is also influenced by p21-activated kinase 1 (Pak1) signaling, we investigated Pak1's potential mechanistic role in the regulation of Snail functions...
  98. ncbi p21-activated Kinase 1 (Pak1)-dependent phosphorylation of Raf-1 regulates its mitochondrial localization, phosphorylation of BAD, and Bcl-2 association
    Shenghao Jin
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 280:24698-705. 2005
    ..Here we elucidate the molecular mechanism through which Pak1 signals to BAD through a Raf-1-activated pathway...
  99. ncbi The active conformation of the PAK1 kinase domain
    Ming Lei
    Laboratory of Molecular Medicine, Children s Hospital, 320 Longwood Avenue, Boston, Massachusetts 02115, USA
    Structure 13:769-78. 2005
    ..A structure of PAK1 in an autoregulated, "off" state showed that a regulatory region, N-terminal to the kinase domain, forces the ..
  100. pmc Active p21-activated kinase 1 rescues MCF10A breast epithelial cells from undergoing anoikis
    Raymond E Menard
    Department of Pharmacology, Wayne State University, 540 East Canfield Avenue, Detroit, MI 48201, USA
    Neoplasia 7:638-45. 2005
    The protein kinase, PAK1, is overexpressed in human breast cancer and may contribute to malignancy through induction of proliferation and invasiveness...
  101. ncbi Angiotensin II-induced activation of p21-activated kinase 1 requires Ca2+ and protein kinase C{delta} in vascular smooth muscle cells
    Elethia A Woolfolk
    Meharry Medical College, Department of Physiology, 1005 DB Todd Blvd, Nashville, TN 37208, USA
    Am J Physiol Cell Physiol 289:C1286-94. 2005
    ..However, the detailed signaling mechanism by which ANG II induces PAK1 activation in VSMCs remains unclear...

Research Grants72

  1. Maria Diakonova; Fiscal Year: 2014
    ..Preliminary data demonstrate that the serine-threonine kinase PAK1 associates with and is Tyr phosphorylated by JAK2...
  2. NEUROFIBROMATOSIS TYPE 1 GENE REGULATES MYELOPOIESIS
    DAVID W CLAPP; Fiscal Year: 2012
    ..We hypothesize that Pak1 functions as a key intracellular signaling pathway node that regulates multiple pathologic mast cell processes...
  3. A novel therapy for HER2 positive hormone refractory breast cancer
    Anne W Hamburger; Fiscal Year: 2010
    ..Further, depletion of EBP1 protein by shRNA or inactivation of EBP1 by phosphorylation by PAK1, a kinase implicated in both breast cancer progression and tamoxifen resistance, results in development of the ..
  4. Jun Li; Fiscal Year: 2016
    ..Moreover, we have shown that removal of the p21-activated kinase type-1 (pak1) gene in PMP22 deficient mice eliminates tomacula/axonal constrictions, a novel signaling mechanism...
  5. Human pathogenic bacterium induces actin phosphorylation to selectively regulate
    Hameeda Sultana; Fiscal Year: 2012
    ..I also show that A. phagocytophilum-induced actin phosphorylation is dependent on Ixodes PAK1-PI3kinase signaling. A...
  6. Post-ischemic cardiac remodeling
    MICHELLE MONASKY; Fiscal Year: 2012
    ..we have previously shown to be cardioprotective during acute ischemia/reperfusion injury is p21-activated kinase 1 (Pak1), a serine/threonine kinase...
  7. CIB1 regulation of endothelial function
    Leslie V Parise; Fiscal Year: 2013
    ..Separate studies have shown that CIB1 binds directly to, and activates, PAK1, a serine/threonine kinase known to regulate endothelial cell migration...
  8. Scott J Russo; Fiscal Year: 2016
    ..are unknown, intracranial injections of the HSV-IKK mutants into the NAc resulted in gross changes in Rac1-PAK1 signaling, a RhoGTPase pathway known to mediate actin cytoskeletal reorganization and the development of new spines...
  9. Gadiparthi N Rao; Fiscal Year: 2016
    ..3. Gab1 targets PAK1 in mediating thrombin-induced HASMC F-actin stress fiber formation, migration, proliferation and neointima ..
  10. Receptor Trafficking in Entry of Murine Leukemia Viruses
    Robert A Davey; Fiscal Year: 2011
    ..Genes corresponding to the Rac1-PAK1-LIMK1 pathway of actin regulation were identified as key for infection by Fr-MLV but not the other viruses...
  11. Benjamin E Turk; Fiscal Year: 2015
    ..Type II PAKs encompass the proteins PAK4, PAK5 and PAK6. Whereas the molecular basis for how type I PAKs (PAK1, PAK2 and PAK3) are regulated by inter- molecular autoinhibition is well established, the type II PAKs are not ..
  12. TROPONIN MODULATION IN HEART FAILURE
    Beata M Wolska; Fiscal Year: 2013
    ..by applicant): In experiments proposed here we test the hypothesis that signaling through p21 activated kinase (Pak1) to protein phosphatase 2A (PP2A) is a novel mechanism of control of contractility by suppression of Ca-release ..
  13. Satya P Kunapuli; Fiscal Year: 2016
    ..We propose to evaluate the role of PAK in translocation of Akt to the membrane using pharmacological approaches and PAK1 and 2 knockout mice...
  14. Rakesh Kumar; Fiscal Year: 2014
    ..molecule known to cause progression of breast cancer cells to more invasive phenotypes is p21-activated kinase 1 (Pak1), a nodular kinase activated by a variety of cell surface or intracellular signals...
  15. Gadiparthi N Rao; Fiscal Year: 2016
    ..NFATc1-cyclin D1-dependent activation of protein kinase C-related kinase 1 (PRK1) and p21-activated kinase 1 (PAK1) and 3. Smooth muscle (SM)-NFATc1 mediates vascular wall remodeling...
  16. Role of the serine-threonine kinase PAK1 in prolactin-dependent signaling
    Maria Diakonova; Fiscal Year: 2007
    ..Preliminary data demonstrate that the serine-threonine kinase PAK1 associates with and is Tyr phosphorylated by JAK2...
  17. Robert A Sweet; Fiscal Year: 2016
    ..spines are reduced in subjects with AD+P in comparison to subjects with AD-P;3) Effectors of LTP (Kalirin7 and PAK1) are reduced, and an effector of LTD (Calcineurin) is elevated, in AD+P compared to AD-P subjects;and 4) increased ..
  18. Role of PAK1-MORC2 Pathway in Breast Cancer
    Rakesh Kumar; Fiscal Year: 2010
    ..It is our hope that the knowledge gained from this project will form the basis for new mechanistic advances in DNAdamage response in breast cancer cells. ..
  19. REGULATION OF NEUTROPHIL RECEPTOR G PROTEIN INTERACTIONS
    Gary Bokoch; Fiscal Year: 2009
    ..We identified molecular targets for cytoskeletal regulation by PAK1, including GEF-H1, LIM kinase, and myosin light chain kinase...
  20. Signaling by p21-activated protein kinases
    JONATHAN D CHERNOFF; Fiscal Year: 2010
    ..The use of a specific Pak inhibitor, as well as cells derived from our recently constructed Pak1 and Pak2 knock-out mice, give us unique reagents with which to accomplish these goals...
  21. Coordination of signaling during phagocytosis
    Joel A Swanson; Fiscal Year: 2010
    ..protein (YFP) chimeras of actin, PI3K, the lipid phosphatase SHIP-1, Rac1, Cdc42, the p21- binding domain of Pak1, and 3'PI-binding domains from signaling proteins...
  22. Identification of Binding Proteins of the Xenopus Morphogenetic Factor Tumorhead
    Edwin E Traverso; Fiscal Year: 2012
    ..Recent studies suggest that TH sub-cellular localization is regulated by Xenopus p21-activated kinase 1 (X-PAK1), whose overexpression is also associated with tumor growth...
  23. Ulrich G Steidl; Fiscal Year: 2016
    ..common disease alleles, including FLT3-ITD and CBFB-MYH11, and through specific HLX-dependent pathways, including PAK1 and BTG1...
  24. Richard L Klemke; Fiscal Year: 2016
    ..amplify tyrosine kinase activity in the cell leading to activation of the canonical ErbB2/Src/p130CAS/c-CrkII/Rac/Pak1/MEK/ERK pathway, which modulates cytoskeletal and integrin functions to drive cell locomotion, invasion, and ..
  25. PAK1's role in eotaxin-mediated murine eosinophil migration
    Muithi M Mwanthi; Fiscal Year: 2012
    ..Through actin-binding effectors, PAK1 modulates the actin cytoskeleton in mast cell degranulation, and additionally we have shown that this isoform is ..
  26. Novel therapeutic targets for Leukemia in Elderly
    Holly Martin; Fiscal Year: 2013
    ..Accordingly, I hypothesized that effectors of the PI3K signaling pathway, in particular p21 activated kinase (PAK1) and its upstream effectors including guanine exchange factors (GEF) and Rho family GTPases contribute to gain-of-..
  27. The Role of the Cdc42-Pak1 Signaling Pathway in the Incretin Effect
    STEPHANIE MICHELLE YODER; Fiscal Year: 2013
    ..Toward this, the involvement of a new signaling axis involving Cdc42-Pak1 proteins in regulating insulin-induced GLP-1 secretion in vitro was recently revealed...
  28. JONATHAN D CHERNOFF; Fiscal Year: 2016
    ..vitro;and 3) We will cross Krox20-cre/Nf1flox/- mice, which develop malignant peripheral nerve sheath tumors, with Pak1 knock out mice, or transplant such NF1 mice with Pak1-/- bone marrow cells, to determine if loss of Pak1, globally ..
  29. Proteolytic Pathways in Progression of Pre-Malignant Breast Disease
    Bonnie F Sloane; Fiscal Year: 2013
    ..Aberrant signal transduction, for example through p21-activated kinase 1 [PAK1], may contribute to increased pericellular proteolysis...
  30. AJAY NMN RANA; Fiscal Year: 2016
    ..via MLK3, we observed a strong interaction between mammalian homolog of yeast Ste20 member, p21 activated kinase (Pak1) and MLK3...
  31. Intracellular signaling by DSCAM during retinal development
    Andrew Garrett; Fiscal Year: 2012
    ..There are a few proteins known to interact with the Dscams: Pak1 (p21-activated kinase) can be activated by Dscam, and the MAGI (membrane- associated guanylate kinase with inverted ..
  32. Regulation of epithelial contact inhibition by Rac effector proteins
    MIRJAM M ZEGERS; Fiscal Year: 2010
    ..defined here as "Pak:PIX complexes", minimally contain the Rac/cdc42 effector molecules p21-activated kinase 1 (Pak1) and the Rac/cdc42-guanine exchange factor betaPIX...
  33. Anand K Ganesan; Fiscal Year: 2016
    ..These studies determined that RhoJ and its downstream kinase PAK1 suppress pathways in melanoma cells that sense DNA damage...
  34. Adam I Marcus; Fiscal Year: 2015
    ..we have published that STRAD1-LKB1 interact with the canonical cell polarity and motility proteins cdc42-PAK1. We build upon this data to determine whether STRAD1-LKB1 regulate vimentin through cdc42-PAK1...
  35. Real-time detection of cancer biomarkers using a self-sustained aptazyme
    Charles Olea; Fiscal Year: 2013
    ..two aptazymes specific for cancer biomarkers prostate-specific antigen (PSA) and p21-activated kinase (PAK1) will be developed...
  36. FUNCTION OF THE VAV PROTOONCOGENE
    Arthur Weiss; Fiscal Year: 2004
    ..might regulate TCR signaling function, we focused on one of their downstream effectors, the serine/threonine kinase Pak1. We found that Pak1 is activated by TCR stimulation and that it contributes to TCR-induced transcriptional ..
  37. The role of Pak1 in regulating plexiform neurofibroma formation
    Andrew McDaniel; Fiscal Year: 2009
    The objective of this application is to identify the role of p21-Activated Kinase 1 (Pak1) in molecular pathways responsible for specific cellular and biochemical phenotypes associated with plexiform neurofibroma formation resulting from ..
  38. MOLECULAR GENETIC ALTERATIONS IN MALIGNANT MESOTHELIOMA
    JOSEPH TESTA; Fiscal Year: 2006
    ..with NF2 inactivation, determine how merlin function is modulated by phosphorylation as an effector of Rac/Cdc42/Pak1 signaling and whether merlin expression/phosphorylation alters downstream signaling involving JNK and AP-1...
  39. DETERMINANTS OF TISSUE ESTRADIOL SENSITIVITY
    Richard Santen; Fiscal Year: 2009
    ..We will test the hypothesis that non-genomic effects of estradiol act through the Rac/PAK1 pathways to enhance the formation of membrane changes to increase motility and invasiveness of breast cancer cells...
  40. REGULATION OF A C JUN KINASE BY A NOVEL TUMOR PROMOTER
    ELIZABETH WATTENBERG; Fiscal Year: 2001
    ..of all or part of a protein kinase cascade that has recently been shown to regulate JNK activation (the Rac, Cdc42/Pak1/MEKK1/SEK1/JNK pathway). Specific Aim 3. Determine if palytoxin stimulates c-Jun transcriptional activity via JNK...
  41. REGULATION OF ENDOCYTIC TRAFFIC IN KIDNEY CELLS
    Gerard Apodaca; Fiscal Year: 2005
    ..It is hypothesized that these novel effectors will regulate endocytic traffic downstream of RhoB. ..
  42. NAK, A POTENTIAL THERAPEUTIC TARGET FOR AIDS
    Arie Abo; Fiscal Year: 2000
    ..Our preliminary results suggest that NAK is co-purified with Pak1 and Nef interacts with Pak1 in-vitro and in-vivo...
  43. Protection Against Apoptosis by Scatter Factor
    Eliot Rosen; Fiscal Year: 2006
    ..period, we found that: 1) the SF protection involves signaling from c-Met -> p21Ras/PI3 kinase -> c-Akt/Pak1 -> forkhead FKHR; 2) the Grb2-associated binder Gab1, an adapter that transduces epithelial morphogenesis, ..
  44. Role of Racl in Regulated Exocytosis
    EDWARD STUENKEL; Fiscal Year: 2004
    ..the role of p35/cyclin dependent kinase 5, an interacting protein kinase that regulates PAK activation, on Rac1 and PAK1 regulation of secretory responsiveness, and 4) To determine the role of Rac1 on phosphatidylinositol 4-phosphate 5- ..
  45. Cytoskeletal Regulation of Outer Hair Cell Motility
    Federico Kalinec; Fiscal Year: 2007
    ..low and auditory frequencies, by addressing the following Specific Aims: 1 - Determine the role of the Rac1-Cdc42/PAK1/LIMK1/cofilin signaling pathway in the regulation of OHC motility, and its interaction with the RhoA/ROCK/LIMK2/..
  46. REGULATION OF P21-ACTIVATED KINASES
    Jonathan Chernoff; Fiscal Year: 2004
    ..We have created two unique reagents: Pak1 mutants that selectively couple to a single GTPase, and phosphorylation-state specific antibodies that recognize ..
  47. AKT1 Oncogene in Carcinogenesis
    Jin Cheng; Fiscal Year: 2005
    ..Based on these data, we hypothesize that that activated AKT1 and its associated proteins are cross-talk with PAK1 and p21 WAFi pathways to contribute to the control of malignant transformation, cell cycle progression and ..
  48. PKA and PAK in Adhesion Dependent Signal Transduction
    Alan Howe; Fiscal Year: 2005
    ....
  49. Mechanism of HIV 1 Nef Action
    BORIS PETERLIN; Fiscal Year: 2006
    ..3 kinase, the guanine nucleotide exchange factor Vav, small GTPases Cdc42 and Racl, and p21 activated kinases, PAK1 and 2...
  50. Pak1 - PIN Pathway in Breast Cancer Progression
    Rakesh Kumar; Fiscal Year: 2008
    ..As described below, our recent work indicate that growth factor-stimulation of p21-activated kinase (Pak1), a serine/threonine kinase, plays a significant role in the cell motility, invasiveness and survival, all of which ..
  51. Pak1 Regulation of Cardiac Protein Phosphorylation
    Katherine Sheehan; Fiscal Year: 2005
    ..phosphorylation of cTnl, MyBP-C, and PLB in isolated rat cardiac ventricular myocytes following activation of the Pak1 pathway by the agonists bradykinin (BK) and lysophosphatidic acid (LPA) or by adenoviral-mediated over-expression ..
  52. Role of JAK2-PAK1 interaction in human breast cancer
    Maria Diakonova; Fiscal Year: 2008
    ..Two proteins - JAK2 and PAK1-have been implicated in breast cancer...
  53. Respiratory syncytial virus targets rafts for penetration and immunomodulation
    HOMERO GABRIEL SAN JUAN VERGARA; Fiscal Year: 2010
    ..8% of the new cases of lower tract respiratory illness in infants. Understanding the mechanistic process of the RSV infection will help in the development of the vaccines and therapies. ..
  54. Transcription Factors & Inflammatory Mediators in Stroke
    Raghu Vemuganti; Fiscal Year: 2007
    ..The ultimate goal is to define the role of SOCS-3/STAT-3 in post-ischemic cerebral inflammation. ..
  55. Microecology-murine gut-initiation & progression of IBD
    James Fox; Fiscal Year: 2005
    ..prior and subsequent to oral vaccination with Helicobacter spp. antigens and mucosal adjuvants, elucidate how these vaccine strategies influence microflora dynamics and impact gut cytokine responses. ..
  56. CD44-P185HER2 INTERACTION IN OVARIAN CANCER PROGRESSION
    LILLY BOURGUIGNON; Fiscal Year: 2007
    ..abstract_text> ..
  57. Injury - Induced Endothelial Dysfunction
    Fiemu Nwariaku; Fiscal Year: 2008
    ..The overall objectives are to determine the role of intracellular oxidants, rho and MAPK pathways on junctional phosphorylation and endothelial dysfunction. [unreadable] [unreadable]..
  58. REGULATION OF HUMAN PHAGOCYTE FUNCTION BY RAC PROTEINS
    Ulla Knaus; Fiscal Year: 2006
    ..These studies will yield novel insights into the overall control of oxidant formation by innate immune cells. ..
  59. BASIS OF SYNAPTIC PATHOLOGY IN ALZHEIMERS DISEASE
    Eliezer Masliah; Fiscal Year: 2001
    ..These studies will help to better understand the mechanisms of synaptic pathology in AD and to develop potential neuroprotective agents that will operate by enhancing the GT activity. ..
  60. Role of Egr-1 in post-stroke inflammation & brain damage
    Raghu Vemuganti; Fiscal Year: 2009
    ..The ultimate goal is to define the role of EgM and its regulators to develop therapies to control cerebral inflammation at the level of transcription. ..
  61. Priscilla A Furth; Fiscal Year: 2016
    ..Pathophysiological changes will be followed in vivo in real-time using ultrasonography and green flourescent protein-based technology. ..
  62. Role of Prostaglandins & Phospholipase A in melanocytes
    Glynis Scott; Fiscal Year: 2009
    ..We hypothesize that PG and phospholipases stimulate HM dendricity, MS transfer &pigmentation through different mechanisms that act synergistically to modulate cutaneous pigmentation following UVR. ..
  63. Rhesus Embryonic Stem Cell-Derived Serotonin Neurons
    CYNTHIA BETHEA; Fiscal Year: 2007
    ..The knowledge obtained from this work will lead to novel treatments for psychoneuropathologies. [unreadable] [unreadable]..
  64. Role of Vav family proteins in cell signaling and cancer
    XOSE BUSTELO; Fiscal Year: 2009
    ..abstract_text> ..
  65. Role of RNA Polymerase II Holoenzyme in Regulation
    Marian Carlson; Fiscal Year: 2004
    ..The proposed studies will further our understanding of the functional interactions of RNA polymerase II holoenzymes with regulatory proteins and signal transduction pathways. ..
  66. Molecular mechanisms of airway smooth muscle function
    Dale Tang; Fiscal Year: 2007
    ..The knowledge obtained from these studies may disclose new biological targets for the development of more effective pharmacological treatment of pulmonary diseases such as asthma. ..
  67. Mechanochemical regulation of endothelial permeability
    Konstantin Birukov; Fiscal Year: 2007
    ....
  68. OVARIAN STEROID REGULATION OF SEROTONIN IN PRIMATES
    CYNTHIA LOUISE BETHEA; Fiscal Year: 2010
    ..Altogether, we will show that ovarian steroids support serotonin neuron survival and we will provide pivotal underlying genomic mechanisms. ..
  69. Reactive Oxygen Species in Anti-Viral Airway Host Defense
    Jeffrey Friedman; Fiscal Year: 2008
    ..Our studies will show if oxidases are a promising target for therapeutic drug development. [unreadable] [unreadable] [unreadable] [unreadable]..
  70. Robert A Rissman; Fiscal Year: 2015
    ..abstract_text> ..
  71. Yeast Genetic Selection for Human AMPK Kinases
    Marian Carlson; Fiscal Year: 2006
    ..Hence, AMPKKs are potentially more specific therapeutic targets for treatment of diabetes and obesity than AMPK. [unreadable] [unreadable]..