Lck

Summary

Gene Symbol: Lck
Description: LCK proto-oncogene, Src family tyrosine kinase
Alias: IMD22, LSK, YT16, p56lck, pp58lck, T-lymphocyte specific protein tyrosine kinase p56lck, leukocyte C-terminal Src kinase, lymphocyte cell-specific protein-tyrosine kinase, lymphocyte-specific protein tyrosine kinase, p56(LSTRA) protein-tyrosine kinase, proto-oncogene tyrosine-protein kinase LCK, t cell-specific protein-tyrosine kinase
Species: human

Top Publications

  1. pmc HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4+ T cells
    Metka Lenassi
    Departments of Medicine, Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA
    Traffic 11:110-22. 2010
  2. ncbi Structural basis for activation of human lymphocyte kinase Lck upon tyrosine phosphorylation
    H Yamaguchi
    Department of Biochemistry and Molecular Biophysics, Columbia University, New York 10032, USA
    Nature 384:484-9. 1996
  3. pmc Proline residues in CD28 and the Src homology (SH)3 domain of Lck are required for T cell costimulation
    A D Holdorf
    Department of Pathology, Center for Immunology, Pulmonary Division, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Exp Med 190:375-84. 1999
  4. ncbi Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation
    Emil H Palacios
    Rosalind Russell Medical Research Center for Arthritis, Department of Medicine and The Howard Hughes Medical Institute, University of California, San Francisco 94143 0795, USA
    Oncogene 23:7990-8000. 2004
  5. ncbi Specific dephosphorylation of the Lck tyrosine protein kinase at Tyr-394 by the SHP-1 protein-tyrosine phosphatase
    G G Chiang
    Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    J Biol Chem 276:23173-8. 2001
  6. ncbi The tyrosine kinase Hck is an inhibitor of HIV-1 replication counteracted by the viral vif protein
    G Hassaine
    INSERM Unit 372, Universite de la Mediterranee, 163 Avenue de Luminy, 13276 Marseilles Cedex 09, France
    J Biol Chem 276:16885-93. 2001
  7. ncbi Intracellular signaling mechanisms leading to synergistic effects of endothelin-1 and stem cell factor on proliferation of cultured human melanocytes. Cross-talk via trans-activation of the tyrosine kinase c-kit receptor
    G Imokawa
    Kao Biological Science Laboratories, Haga, Tochigi 321 3497, Japan
    J Biol Chem 275:33321-8. 2000
  8. pmc Expression of the p56(Lck) Y505F mutation in CD45-deficient mice rescues thymocyte development
    J R Seavitt
    Center for Immunology, Department of Pathology and Howard Hughes Medical Institute, Washington University, St Louis, Missouri 63110, USA
    Mol Cell Biol 19:4200-8. 1999
  9. ncbi Superantigen stimulation reveals the contribution of Lck to negative regulation of T cell activation
    Gabriel Criado
    FOCIS Center for Clinical Immunology and Immunotherapeutics, Robarts Research Institute, 100 Perth Drive, London, Ontario, Canada N6A 5K8
    J Immunol 172:222-30. 2004
  10. doi Reduced Cbl phosphorylation and degradation of the zeta-chain of the T-cell receptor/CD3 complex in T cells with low Lck levels
    Trond Methi
    The Biotechnology Centre of Oslo and Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, Oslo, Norway
    Eur J Immunol 38:2557-63. 2008

Detail Information

Publications254 found, 100 shown here

  1. pmc HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4+ T cells
    Metka Lenassi
    Departments of Medicine, Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA
    Traffic 11:110-22. 2010
    ..Thus, HIV-infected cells export Nef in bioactive vesicles, which facilitate the depletion of CD4(+) T cells that is a hallmark of acquired immunodeficiency syndrome (AIDS)...
  2. ncbi Structural basis for activation of human lymphocyte kinase Lck upon tyrosine phosphorylation
    H Yamaguchi
    Department of Biochemistry and Molecular Biophysics, Columbia University, New York 10032, USA
    Nature 384:484-9. 1996
    Regulation through phosphorylation is a characteristic of signalling pathways and the lymphocyte kinase Lck (p56lck) both performs phosphorylation and is affected by it...
  3. pmc Proline residues in CD28 and the Src homology (SH)3 domain of Lck are required for T cell costimulation
    A D Holdorf
    Department of Pathology, Center for Immunology, Pulmonary Division, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Exp Med 190:375-84. 1999
    The Src family tyrosine kinases Lck and Fyn are critical for signaling via the T cell receptor. However, the exact mechanism of their activation is unknown...
  4. ncbi Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation
    Emil H Palacios
    Rosalind Russell Medical Research Center for Arthritis, Department of Medicine and The Howard Hughes Medical Institute, University of California, San Francisco 94143 0795, USA
    Oncogene 23:7990-8000. 2004
    The function of the Src-family kinases (SFKs) Lck and Fyn in T cells has been intensively studied over the past 15 years...
  5. ncbi Specific dephosphorylation of the Lck tyrosine protein kinase at Tyr-394 by the SHP-1 protein-tyrosine phosphatase
    G G Chiang
    Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    J Biol Chem 276:23173-8. 2001
    ..In this study, we demonstrate that SHP-1 dephosphorylates the lymphoid-specific Src family kinase Lck at Tyr-394 when both are transiently co-expressed in nonlymphoid cells...
  6. ncbi The tyrosine kinase Hck is an inhibitor of HIV-1 replication counteracted by the viral vif protein
    G Hassaine
    INSERM Unit 372, Universite de la Mediterranee, 163 Avenue de Luminy, 13276 Marseilles Cedex 09, France
    J Biol Chem 276:16885-93. 2001
    ..Hck, which is present in monocyte-macrophage cells, represents the first identified cellular inhibitor of HIV-1 replication overcome by Vif...
  7. ncbi Intracellular signaling mechanisms leading to synergistic effects of endothelin-1 and stem cell factor on proliferation of cultured human melanocytes. Cross-talk via trans-activation of the tyrosine kinase c-kit receptor
    G Imokawa
    Kao Biological Science Laboratories, Haga, Tochigi 321 3497, Japan
    J Biol Chem 275:33321-8. 2000
    ....
  8. pmc Expression of the p56(Lck) Y505F mutation in CD45-deficient mice rescues thymocyte development
    J R Seavitt
    Center for Immunology, Department of Pathology and Howard Hughes Medical Institute, Washington University, St Louis, Missouri 63110, USA
    Mol Cell Biol 19:4200-8. 1999
    ..thymocyte development was due to the inability to dephosphorylate the inhibitory phosphorylation site (Y505) in p56(lck) (Lck), we generated CD45-deficient mice that express transgenes for the Lck Y505F mutation and the DO11...
  9. ncbi Superantigen stimulation reveals the contribution of Lck to negative regulation of T cell activation
    Gabriel Criado
    FOCIS Center for Clinical Immunology and Immunotherapeutics, Robarts Research Institute, 100 Perth Drive, London, Ontario, Canada N6A 5K8
    J Immunol 172:222-30. 2004
    The conventional paradigm of T cell activation through the TCR states that Lck plays a critical activating role in this signaling process. However, the T cell response to bacterial superantigens does not require Lck...
  10. doi Reduced Cbl phosphorylation and degradation of the zeta-chain of the T-cell receptor/CD3 complex in T cells with low Lck levels
    Trond Methi
    The Biotechnology Centre of Oslo and Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, Oslo, Norway
    Eur J Immunol 38:2557-63. 2008
    T cells with short interfering RNA-mediated Lck-knockdown (kd) display paradoxical hyper-responsiveness upon TCR ligation...
  11. ncbi The human immunodeficiency virus type 1 Nef protein binds the Src-related tyrosine kinase Lck SH2 domain through a novel phosphotyrosine independent mechanism
    H Dutartre
    Unité 119 Instituto National de la Santé et de la Recherche Médicale, Marseille, France
    Virology 247:200-11. 1998
    ..infected monocytes, we and others have reported previously that Nef also interacts with the T-lymphocyte Src-kinase Lck, leading to specific cell signaling impairment...
  12. pmc Repression of human immunodeficiency virus type 1 long terminal repeat-driven gene expression by binding of the virus to its primary cellular receptor, the CD4 molecule
    P Berube
    Centre de Recherche en Infectiologie, Centre hospitalier de l Universite Laval, Quebec, Canada
    J Virol 70:4009-16. 1996
    ..The virus-mediated signal transduction was shown to be mediated via p56lck-dependent and -independent pathways...
  13. ncbi The role of C-terminal tyrosine phosphorylation in the regulation of SHP-1 explored via expressed protein ligation
    Zhongsen Zhang
    Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Biol Chem 278:4668-74. 2003
    ....
  14. pmc Identification of a highly conserved valine-glycine-phenylalanine amino acid triplet required for HIV-1 Nef function
    Pieter J Meuwissen
    Department of Clinical Chemistry, Microbiology, and Immunology, Ghent University, Ghent, B 9000, Belgium
    Retrovirology 9:34. 2012
    ..In this study, we aimed to study the functional importance of this VGF region...
  15. ncbi In vitro tyrosine phosphorylation of PLC-gamma 1 and PLC-gamma 2 by src-family protein tyrosine kinases
    F Liao
    Department of Molecular Biology and Genetics, Johns Hopkins University, School of Medicine, Baltimore, MD 21205
    Biochem Biophys Res Commun 191:1028-33. 1993
    ..of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro...
  16. pmc Tyrosine phosphorylation sites at amino acids 239 and 240 of Shc are involved in epidermal growth factor-induced mitogenic signaling that is distinct from Ras/mitogen-activated protein kinase activation
    N Gotoh
    Department of Genetics, Institute of Medical Science, University of Tokyo, Japan
    Mol Cell Biol 17:1824-31. 1997
    ..These results suggest that Shc activates two distinct signaling pathways, Y317 to Ras/MAPK and Y239 and Y240 to another pathway including Myc, and that both are involved in EGF-induced mitogenic signaling...
  17. ncbi Human homologue of the Drosophila discs large tumor suppressor binds to p56lck tyrosine kinase and Shaker type Kv1.3 potassium channel in T lymphocytes
    T Hanada
    Laboratory of Tumor Cell Biology, St Elizabeth s Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02135, USA
    J Biol Chem 272:26899-904. 1997
    ..Immunoblotting experiments revealed that the immunoprecipitates of hDlg contain p56lck, a member of the Src family of tyrosine kinases...
  18. pmc Phosphatidylinositol (PI) 3-kinase and PI 4-kinase binding to the CD4-p56lck complex: the p56lck SH3 domain binds to PI 3-kinase but not PI 4-kinase
    K V Prasad
    Division of Tumor Immunology, Dana Farber Cancer Institute, Boston, Massachusetts 02115
    Mol Cell Biol 13:7708-17. 1993
    ..It is coupled to the protein-tyrosine kinase p56lck, an interaction necessary for an optimal response of certain T cells to antigen...
  19. ncbi Profound block in thymocyte development in mice lacking p56lck
    T J Molina
    Ontario Cancer Institute, University of Toronto, Canada
    Nature 357:161-4. 1992
    The protein Lck (p56lck) has a relative molecular mass of 56,000 and belongs to the Src family of tyrosine kinases. It is expressed exclusively in lymphoid cells, predominantly in thymocytes and peripheral T cells...
  20. ncbi RT loop flexibility enhances the specificity of Src family SH3 domains for HIV-1 Nef
    S Arold
    Centre de Biochimie Structurale, UMR C9955 CNRS, U414 INSERM, Universite Montpellier 1, France
    Biochemistry 37:14683-91. 1998
    ..is approximately an order of magnitude tighter than those of other Src family kinases that were investigated (Fyn, Lck, and Src)...
  21. doi Uncoordinated 119 protein controls trafficking of Lck via the Rab11 endosome and is critical for immunological synapse formation
    Magdalena M Gorska
    Division of Allergy and Immunology, Department of Medicine, National Jewish Health, Denver, CO 80206, USA
    J Immunol 183:1675-84. 2009
    ..any enzymatic activity and relies on the plasma membrane-associated lymphocyte-specific protein tyrosine kinase (Lck) for initiation of signaling. Here we uncover a mechanism that is responsible for plasma membrane targeting of Lck...
  22. ncbi A weak Lck tail bite is necessary for Lck function in T cell antigen receptor signaling
    Konstantina Nika
    Program on Inflammatory Disease Research, Infectious and Inflammatory Disease Center, The Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Biol Chem 282:36000-9. 2007
    ..understand the relative importance of these two opposite functions of the SH2 domain of the Src family kinase Lck in TCR signaling, we created three mutants of Lck in which the intramolecular binding of the C terminus to the SH2 ..
  23. ncbi Hypoxia regulates cross-talk between Syk and Lck leading to breast cancer progression and angiogenesis
    Goutam Chakraborty
    National Center for Cell Science, Pune 411 007, India
    J Biol Chem 281:11322-31. 2006
    ..The nonreceptor protein-tyrosine kinases Syk and Lck play crucial roles in the signaling mechanism of various cellular processes...
  24. ncbi Tyrosine 319 in the interdomain B of ZAP-70 is a binding site for the Src homology 2 domain of Lck
    M Pelosi
    Molecular Immunology Unit, Institut Pasteur, 25 28 Rue du Docteur Roux, 75724 Paris Cedex 15, France
    J Biol Chem 274:14229-37. 1999
    T-cell antigen receptor-induced signaling requires both ZAP-70 and Lck protein-tyrosine kinases. One essential function of Lck in this process is to phosphorylate ZAP-70 and up-regulate its catalytic activity...
  25. ncbi Phosphorylation of SLP-76 by the ZAP-70 protein-tyrosine kinase is required for T-cell receptor function
    J Bubeck Wardenburg
    Center for Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 271:19641-4. 1996
    ..As SLP-76 interacts with both Grb2 and phospholipase C-gamma1, these data indicate that phosphorylation of SLP-76 by ZAP-70 provides an important functional link between the T-cell receptor and activation of ras and calcium pathways...
  26. pmc Structure function analysis of SH2D2A isoforms expressed in T cells reveals a crucial role for the proline rich region encoded by SH2D2A exon 7
    Stine Granum
    Department of Anatomy, Institute of Basic Medical Sciences, Box 1105, Blindern, N 0317 Oslo, Norway
    BMC Immunol 7:15. 2006
    The activation induced T cell specific adapter protein (TSAd), encoded by SH2D2A, interacts with and modulates Lck activity. Several transcript variants of TSAd mRNA exist, but their biological significance remains unknown...
  27. pmc Constitutively active Lck kinase in T cells drives antigen receptor signal transduction
    Konstantina Nika
    T Cell Signaling Laboratory, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK
    Immunity 32:766-77. 2010
    ..TCR) and coreceptor ligation is thought to initiate signal transduction by inducing activation of the kinase Lck. Here we showed that catalytically active Lck was present in unstimulated naive T cells and thymocytes and was ..
  28. doi HIV-1 Nef compensates for disorganization of the immunological synapse by inducing trans-Golgi network-associated Lck signaling
    Xiaoyu Pan
    Department of Infectious Diseases, Virology, University Hospital Heidelberg, Germany
    Blood 119:786-97. 2012
    ..Nef reroutes kinase-active pools of the TCR signaling master switch Lck away from the plasma membrane (PM) to the trans-Golgi network (TGN), thereby preventing the recruitment of active ..
  29. pmc Direct observation and quantitative analysis of Lck exchange between plasma membrane and cytosol in living T cells
    Lars Zimmermann
    Biophysics Institute, Johannes Kepler University Linz, Altenbergerstrasse 69, A 4040 Linz, Austria
    J Biol Chem 285:6063-70. 2010
    ..for quantifying the exchange kinetics of plasma membrane and cytosolic populations of fluorescently labeled Lck, the key Src family kinase involved in early T cell signaling...
  30. ncbi Induction of HIV transcription by Nef involves Lck activation and protein kinase C theta raft recruitment leading to activation of ERK1/2 but not NF kappa B
    Vanessa Witte
    Otto von Guericke University of Magdeburg, Institute of Molecular and Clinical Immunology, Magdeburg, Germany
    J Immunol 181:8425-32. 2008
    ..Previously, we have shown that Nef enhances Tat-mediated transcription in a manner depending on Lck and the cytoplasmic sequestration of the transcriptional repressor embryonic ectodermal development [corrected]...
  31. ncbi The N-terminus of Nef from HIV-1/SIV associates with a protein complex containing Lck and a serine kinase
    A S Baur
    Institut fur Klinische und Molekulare Virologie, Universitat Erlangen Nurnberg, Erlangen, Federal Republic of Germany
    Immunity 6:283-91. 1997
    ..One of the kinases was identified as Lck, whereas the second protein was found to be a serine kinase that phosphorylated Nef and Lck in vitro and could be ..
  32. pmc Human immunodeficiency virus type 1 Nef binds directly to Lck and mitogen-activated protein kinase, inhibiting kinase activity
    A Greenway
    AIDS Cellular Biology Unit, Macfarlane Burnet Centre for Medical Research, Fairfield, Victoria, Australia
    J Virol 70:6701-8. 1996
    ..specific cellular proteins involved in signal transduction, including at least a member of the src family kinase, Lck, and the serine/threonine kinase, mitogen-activated protein kinase (MAPK)...
  33. pmc HIV-1 Nef employs two distinct mechanisms to modulate Lck subcellular localization and TCR induced actin remodeling
    Claudia Haller
    Abteilung Virologie, Universitatsklinikum Heidelberg, Heidelberg, Germany
    PLoS ONE 2:e1212. 2007
    ..spreading and actin polymerization upon TCR engagement, a pronounced intracellular accumulation of the Src kinase Lck and its reduced IS recruitment...
  34. doi Modulation of Lck function through multisite docking to T cell-specific adapter protein
    Stine Granum
    Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Box 1105, Blindern, N 0317 Oslo, Norway
    J Biol Chem 283:21909-19. 2008
    T cell-specific adapter protein (TSAd), encoded by the SH2D2A gene, interacts with Lck through its C terminus and thus modulates Lck activity...
  35. ncbi Lck phosphorylates the activation loop tyrosine of the Itk kinase domain and activates Itk kinase activity
    S D Heyeck
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
    J Biol Chem 272:25401-8. 1997
    ..tyrosine-phosphorylated after TCR cross-linking and that this phosphorylation depends on the presence of functional Lck. To determine if this Lck dependence results from direct phosphorylation of Itk by Lck, we generated recombinant ..
  36. ncbi Mapping the binding site of full length HIV-1 Nef on human Lck SH3 by NMR spectroscopy
    Lars Briese
    Institut fur Molekulare Biotechnologie, 07745, Jena, Germany
    J Biomed Sci 12:451-6. 2005
    ..virus type 1 (HIV-1) is known to directly bind to the SH3 domain of human lymphocyte specific kinase (Lck) via a proline-rich region located in the amino terminal part of Nef...
  37. ncbi No association between lck gene polymorphisms and protein level in type 1 diabetes
    Solange Nervi
    Universite de la Mediterranee, CHU Sainte Marguerite, Marseille, France
    Diabetes 51:3326-30. 2002
    We previously described a reduced expression of the protein tyrosine kinase Lck in T-cells from type 1 diabetic patients, the origin of which is still unknown. The human lck gene, located on chromosome 1p35-34...
  38. ncbi The anti-apoptotic effect of Notch-1 requires p56lck-dependent, Akt/PKB-mediated signaling in T cells
    Hadassah Sade
    National Centre for Biological Sciences, University of Agricultural Sciences Gandhi Krishi Vignan Kendra Campus, New Bellary Road, Bangalore 560065, Karnataka, India
    J Biol Chem 279:2937-44. 2004
    ..Using a cell line deficient for the T cell-specific, Src family protein, the tyrosine kinase p56(lck) and by reconstitution approaches we demonstrate that p56(lck) is required for the Notch-1-mediated activation of ..
  39. pmc Regulation of Fyn through translocation of activated Lck into lipid rafts
    Dominik Filipp
    Sunnybrook and Women s College Health Sciences Centre, and Departmentof Immunology, University of Toronto, Ontario M4N 3M5, Canada
    J Exp Med 197:1221-7. 2003
    Whether or how the activation of Lck and Fyn during T cell receptor (TCR) signaling is coordinated, and their delivery of function integrated, is unknown...
  40. ncbi A requirement for caveolin-1 and associated kinase Fyn in integrin signaling and anchorage-dependent cell growth
    K K Wary
    Cellular Biochemistry and Biophysics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cell 94:625-34. 1998
    ..These findings reveal an unexpected function of caveolin-1 and Fyn in integrin signaling and anchorage-dependent cell growth...
  41. pmc The protein tyrosine kinase p56lck is required for triggering NF-kappaB activation upon interaction of human immunodeficiency virus type 1 envelope glycoprotein gp120 with cell surface CD4
    L Briant
    Laboratoire Infections Retrovirales et Signalisation Cellulaire, CRBM CNRS UPR 1086, Institut de Biologie, Montpellier, France
    J Virol 72:6207-14. 1998
    ..Here we investigate the putative role of p56(lck) as a possible cellular intermediate in this signal transduction pathway...
  42. ncbi Thiol/disulfide exchange is a prerequisite for CXCR4-tropic HIV-1 envelope-mediated T-cell fusion during viral entry
    Ingrid Markovic
    Center for Drug Evaluation and Research, Food and Drug Adminiatration, Bethesda, MD, USA
    Blood 103:1586-94. 2004
    ....
  43. pmc The LIM protein Ajuba influences interleukin-1-induced NF-kappaB activation by affecting the assembly and activity of the protein kinase Czeta/p62/TRAF6 signaling complex
    Yungfeng Feng
    Department of Medicine, Washington University, St Louis, Missouri 63110, USA
    Mol Cell Biol 25:4010-22. 2005
    ..We propose that Ajuba is a new cytosolic component of the IL-1 signaling pathway modulating IL-1-induced NF-kappaB activation by influencing the assembly and activity of the aPKC/p62/TRAF6 multiprotein signaling complex...
  44. pmc SHP2-interacting transmembrane adaptor protein (SIT), a novel disulfide-linked dimer regulating human T cell activation
    A Marie-Cardine
    Immunomodulation Laboratory of the Institute for Immunology, University of Heidelberg, 69120 Heidelberg, Germany
    J Exp Med 189:1181-94. 1999
    ..However, binding of SHP2 to SIT is not required for inhibition of NF-AT induction, suggesting that SIT not only regulates NF-AT activity but also controls NF-AT unrelated pathways of T cell activation involving SHP2...
  45. ncbi Association analysis of the lymphocyte-specific protein tyrosine kinase (LCK) gene in type 1 diabetes
    John S Hulme
    JDRF WT Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, Wellcome Trust MRC Building, Addenbrooke s Hospital, Hills Road, Cambridge, CB2 2XY, UK
    Diabetes 53:2479-82. 2004
    Prior data associating the expression of lymphocyte-specific protein tyrosine kinase (LCK) with type 1 diabetes, its critical function in lymphocytes, and the linkage of the region to diabetes in the nonobese diabetic (NOD) mouse model ..
  46. ncbi HIV type 1 glycoprotein 120 amplifies tumor necrosis factor-induced NF-kappa B activation in Jurkat cells
    V A Shatrov
    Division of Immunochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    AIDS Res Hum Retroviruses 12:1209-16. 1996
    ..In contrast, in the p56lck-deficient J.CaM1...
  47. pmc Binding of human immunodeficiency virus type 1 to CD4 induces association of Lck and Raf-1 and activates Raf-1 by a Ras-independent pathway
    W Popik
    Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
    Mol Cell Biol 16:6532-41. 1996
    ..gp120 to CD4 receptors resulted in association and tyrosine phosphorylation and activation of tyrosine kinase Lck and serine/threonine kinase Raf-1...
  48. pmc T cell receptor (TCR) interacting molecule (TRIM), a novel disulfide-linked dimer associated with the TCR-CD3-zeta complex, recruits intracellular signaling proteins to the plasma membrane
    E Bruyns
    Institute for Immunology, University of Heidelberg, 69120 Heidelberg, Germany
    J Exp Med 188:561-75. 1998
    ..Thus, TRIM represents a TCR-associated transmembrane adaptor protein which is likely involved in targeting of intracellular signaling proteins to the plasma membrane after triggering of the TCR...
  49. ncbi HIV-1 Nef plays an essential role in two independent processes in CD4 down-regulation: dissociation of the CD4-p56(lck) complex and targeting of CD4 to lysosomes
    Y H Kim
    Laboratory of Molecular Virology, Samsung Biomedical Research Institute, Seoul, Korea
    Virology 257:208-19. 1999
    ..in cells lacking p56(lck) expression, but not in cells with p56(lck);these mutants fail to dissociate CD4 from p56lck. These results show that Nef-mediated CD4 dissociation from p56(lck) is important for CD4 down-regulation...
  50. pmc Guanidine alkaloid analogs as inhibitors of HIV-1 Nef interactions with p53, actin, and p56lck
    Allison Olszewski
    Department of Chemistry, University of California, Irvine, CA 92697 2025, USA
    Proc Natl Acad Sci U S A 101:14079-84. 2004
    ..were used to identify a series of guanidine alkaloid-based inhibitors of Nef interactions with p53, actin, and p56(lck)...
  51. ncbi CIN85 associates with TNF receptor 1 via Src and modulates TNF-alpha-induced apoptosis
    Tadashi Narita
    Laboratory of Bacterial Infection and Immunity, Department of Immunology, National Institute of Infectious Diseases, 1 23 1, Toyama, Tokyo 162 8640, Japan
    Exp Cell Res 304:256-64. 2005
    ..TNF-alpha treatment recruited CIN85 to the TNFR1 signaling complex. Taken together, these results indicate that CIN85 associates with TNFR1 via Src and modulates TNF-alpha-induced apoptosis...
  52. pmc Simian immunodeficiency virus and human immunodeficiency virus type 1 nef proteins show distinct patterns and mechanisms of Src kinase activation
    A L Greenway
    AIDS Cellular Biology Unit, Macfarlane Burnet Center for Medical Research, Fairfield, Victoria 3078, Australia
    J Virol 73:6152-8. 1999
    ..We show here that the Nef protein encoded by SIVmac239 interacts with and also activates the human Src kinases Lck and Hck. This is in direct contrast to the inhibitory effect of HIV type 1 (HIV-1) Nef on Lck catalytic activity...
  53. ncbi Differential requirement for p56lck in HIV-tat versus TNF-induced cellular responses: effects on NF-kappa B, activator protein-1, c-Jun N-terminal kinase, and apoptosis
    S K Manna
    Cytokine Research Section, Department of Bioimmunotherapy, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    J Immunol 164:5156-66. 2000
    ..In the present study we investigated the role of the T cell-specific tyrosine kinase p56lck in HIV-tat and TNF-mediated cellular responses by comparing the responses of Jurkat T cells with JCaM1 cells, an ..
  54. pmc Proline-rich (PxxP) motifs in HIV-1 Nef bind to SH3 domains of a subset of Src kinases and are required for the enhanced growth of Nef+ viruses but not for down-regulation of CD4
    K Saksela
    Rockefeller University, New York, NY 10021
    EMBO J 14:484-91. 1995
    ..Thus, CD4 down-regulation and promotion of viral growth are two distinct functions of Nef, and the latter is mediated via SH3 binding...
  55. pmc Human immunodeficiency virus type 1 glycoprotein precursor retains a CD4-p56lck complex in the endoplasmic reticulum
    B Crise
    Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510
    J Virol 66:2296-301. 1992
    ..At the plasma membrane of T cells, CD4 is tightly associated with a cytoplasmic tyrosine kinase (p56lck) that is involved in T-cell activation...
  56. ncbi Signal transduction through decay-accelerating factor. Interaction of glycosyl-phosphatidylinositol anchor and protein tyrosine kinases p56lck and p59fyn 1
    A M Shenoy-Scaria
    Department of Pathology, Washington University School of Medicine, St Louis, MO 63110
    J Immunol 149:3535-41. 1992
    ..Both p56lck and p59fyn were associated with DAF in DAF-transfected EL-4 cells...
  57. ncbi A natural variability in the proline-rich motif of Nef modulates HIV-1 replication in primary T cells
    O T Fackler
    Institute for Hygiene, Department of Virology, University of Heidelberg, D 69120, Heidelberg, Germany
    Curr Biol 11:1294-9. 2001
    ..Our report suggests that functionally and conformationally distinct Nef isoforms modulate HIV replication on the interaction level with the TCR-signaling environment once the virus enters the T cell compartment...
  58. pmc The Src kinase Lck facilitates assembly of HIV-1 at the plasma membrane
    Amy B Strasner
    Intergrated Bioscience Program in Immunobiology, Huck Institute of the Life Sciences, Pennsylvania State University, University Park, PA 16802, USA
    J Immunol 181:3706-13. 2008
    ..However, the pathways and cellular mediators of Gag targeting to the plasma membrane are not well characterized. Lck, a lymphoid specific Src kinase critical for T cell activation, is found in the plasma membrane as well as various ..
  59. ncbi HIV-1 glycoprotein gp120 disrupts CD4-p56lck/CD3-T cell receptor interactions and inhibits CD3 signaling
    P Hubert
    Laboratoire d Immunologie Cellulaire et Tissulaire, CNRS URA 625, Paris, France
    Eur J Immunol 25:1417-25. 1995
    ..Additionally, gp120 was shown to dissociate the tyrosine kinase p56lck from CD4 in CEM cells, with a concommittant inhibition of CD4-linked kinase activity...
  60. pmc Identification of preferred protein interactions by phage-display of the human Src homology-3 proteome
    Satu Kärkkäinen
    Institute of Medical Technology, University of Tampere and Tampere University Hospital, Biokatu 8, Tampere 33014, Finland
    EMBO Rep 7:186-91. 2006
    ....
  61. doi Genetically encoded Förster resonance energy transfer sensors for the conformation of the Src family kinase Lck
    Wolfgang Paster
    Department of Molecular Immunology, Center for Physiology, Pathophysiology and Immunology, Medical University of Vienna, Vienna, Austria
    J Immunol 182:2160-7. 2009
    The current model for regulation of the Src family kinase member Lck postulates a strict correlation between structural condensation of the kinase backbone and catalytic activity...
  62. ncbi Binding of HIV-1 to its receptor induces tyrosine phosphorylation of several CD4-associated proteins, including the phosphatidylinositol 3-kinase
    G Briand
    Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Quebec, Canada
    Virology 228:171-9. 1997
    ..Immunoblot analysis permitted the identification of two of these proteins, p56lck and phosphatidylinositol 3-kinase (PI 3-kinase) p85 alpha...
  63. ncbi SHP-1 regulates Lck-induced phosphatidylinositol 3-kinase phosphorylation and activity
    B Cuevas
    Division of Medicine, and the Cell Growth Regulation Laboratory, University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 274:27583-9. 1999
    Ligation of the T cell antigen receptor (TCR) activates the Src family tyrosine kinase p56 Lck, which, in turn, phosphorylates a variety of intracellular substrates...
  64. pmc Dok-3, a novel adapter molecule involved in the negative regulation of immunoreceptor signaling
    S Lemay
    McGill Cancer Centre, McGill University, Montreal, Quebec, Canada H3G 1Y6
    Mol Cell Biol 20:2743-54. 2000
    ....
  65. ncbi Identification of two SH3-binding motifs in the regulatory subunit of phosphatidylinositol 3-kinase
    R Kapeller
    Department of Physiology, Tufts University Medical School, Boston, Massachusetts 02111
    J Biol Chem 269:1927-33. 1994
    ..Here we show that p85, the regulatory subunit of PI 3-kinase, binds directly to the SH3 domains of Abl, Lck, Fyn, and p85 itself...
  66. pmc Regulation of the Src family kinase Lck by Hsp90 and ubiquitination
    Ana Giannini
    Department of Immunobiology, Guy s Hospital, King s College London, United Kingdom
    Mol Cell Biol 24:5667-76. 2004
    Regulation of the Src-related tyrosine kinase Lck is crucial to the outcome of T-cell receptor (TCR) stimulation. It was previously shown that the stability of the constitutively active mutant LckY505F is controlled by Hsp90 (M. J...
  67. ncbi Lck is required for stromal cell-derived factor 1 alpha (CXCL12)-induced lymphoid cell chemotaxis
    Marit Inngjerdingen
    Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Norway
    Blood 99:4318-25. 2002
    ..Damnacanthal, a specific Lck inhibitor, but not the Syk inhibitor piceatannol, inhibited CXCL12-induced chemotaxis of both lymphocyte subsets...
  68. ncbi Lad, an adapter protein interacting with the SH2 domain of p56lck, is required for T cell activation
    Y B Choi
    Signal Transduction Laboratory Mogam Biotechnology Research Institute, Koosungmyon, Yonginsi, Kyunggido, Korea
    J Immunol 163:5242-9. 1999
    T cell-specific Src family tyrosine kinase, p56lck, plays crucial roles in T cell differentiation, activation, and proliferation...
  69. ncbi Activation of phosphatidylinositol-3-kinase in Jurkat T cells depends on the presence of the p56lck tyrosine kinase
    M von Willebrand
    Division of Cell Biology, Institute for Allergy and Immunology, La Jolla, CA 92037
    Eur J Immunol 24:234-8. 1994
    ..tyrosine phosphorylation and activation of PI3K in Jurkat T leukemia cells depend on the presence of the p56lck tyrosine kinase: in a variant of the Jurkat T cell line lacking p56lck, JCaM1, these responses were absent...
  70. pmc Selective interaction of LAT (linker of activated T cells) with the open-active form of Lck in lipid rafts reveals a new mechanism for the regulation of Lck in T cells
    Panagiotis S Kabouridis
    Bone and Joint Research Unit, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, Charterhouse Square, London EC1M 6BQ, UK
    Biochem J 371:907-15. 2003
    In T cells, the lipid raft-associated Lck is strongly tyrosine phosphorylated and has reduced enzymic activity in contrast with the detergent-soluble pool, which has substantial activity...
  71. pmc Unc119, a novel activator of Lck/Fyn, is essential for T cell activation
    Magdalena M Gorska
    Division of Allergy and Immunology, Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555, USA
    J Exp Med 199:369-79. 2004
    The first step in T cell receptor for antigen (TCR) signaling is the activation of the receptor-bound Src kinases, Lck and Fyn. The exact mechanism of this process is unknown...
  72. doi HIV-1 Nef limits communication between linker of activated T cells and SLP-76 to reduce formation of SLP-76-signaling microclusters following TCR stimulation
    Libin Abraham
    Department of Infectious Diseases, Virology, University Hospital Heidelberg, 69120 Heidelberg, Germany
    J Immunol 189:1898-910. 2012
    ..Nef thus employs a dual mechanism to disturb early TCR signaling by limiting the communication between LAT and SLP-76 and preventing the dynamic formation of SLP-76-signaling MCs...
  73. ncbi gp120 ligation of CD4 induces p56lck activation and TCR desensitization independent of TCR tyrosine phosphorylation
    F Goldman
    Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206
    J Immunol 153:2905-17. 1994
    ..Studies reported here reveal that CD4 ligation initiates p56lck activation and renders human peripheral T cells and HPB-ALL cells hyporesponsive to Ag receptor stimulation, as ..
  74. ncbi Cutting edge: the CD45 tyrosine phosphatase is an inhibitor of Lck activity in thymocytes
    U D'Oro
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 162:1879-83. 1999
    A widely accepted model for regulation of the Lck tyrosine kinase is that it is activated by CD45-mediated dephosphorylation of its COOH-terminal negative regulatory tyrosine (Tyr505)...
  75. pmc The T-cell antigen CD5 acts as a receptor and substrate for the protein-tyrosine kinase p56lck
    M Raab
    Division of Tumor Immunology, Dana Farber Cancer Institute, Boston, Massachusetts 02115
    Mol Cell Biol 14:2862-70. 1994
    ..In this study, we demonstrate that CD5 is coupled to the protein-tyrosine kinase p56lck and can act as a substrate for p56lck...
  76. pmc Phosphoprotein associated with glycosphingolipid-enriched microdomains (PAG), a novel ubiquitously expressed transmembrane adaptor protein, binds the protein tyrosine kinase csk and is involved in regulation of T cell activation
    T Brdicka
    Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 14220 Prague, Czech Republic
    J Exp Med 191:1591-604. 2000
    ..These findings collectively suggest that in the absence of external stimuli, the PAG-Csk complex transmits negative regulatory signals and thus may help to keep resting T cells in a quiescent state...
  77. ncbi Inhibition of tyrosine kinase activation blocks the down-regulation of CXC chemokine receptor 4 by HIV-1 gp120 in CD4+ T cells
    S B Su
    Laboratory of Molecular Immunoregulation, Division of Basic Sciences, SAIC Frederick National Cancer Institute, MD 21702, USA
    J Immunol 162:7128-32. 1999
    ..gp120, but not SDF-1alpha, induced rapid tyrosine phosphorylation of src-like kinase p56lck in CD4+ T cells, whereas both gp120 and SDF-1alpha caused phosphorylation of the CXCR4...
  78. ncbi The influence of the src-family kinases, Lck and Fyn, on T cell differentiation, survival and activation
    Rose Zamoyska
    Division of Molecular Immunology, National Institute for Medical Research, London, UK
    Immunol Rev 191:107-18. 2003
    The src-family kinases p56lck (Lck) and p59fyn (Fyn) are expressed in T cells and are among the first signaling molecules to be activated downstream of the T cell receptor (TCR)...
  79. ncbi Molecular cloning of SKAP55, a novel protein that associates with the protein tyrosine kinase p59fyn in human T-lymphocytes
    A Marie-Cardine
    Ruprecht Karls University Heidelberg, Institute of Immunology, 69120 Heidelberg, Germany
    J Biol Chem 272:16077-80. 1997
    ..Consistent with this observation, pp55 selectively binds to isolated SH2 domains of Lck, Lyn, Src, and Fyn but not to the SH2 domains of ZAP70, Syk, Shc, SLP-76, Grb2, phosphatidylinositol 3-kinase, and ..
  80. pmc A 10-aa-long sequence in SLP-76 upstream of the Gads binding site is essential for T cell development and function
    Lalit Kumar
    Division of Immunology, Children s Hospital, CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:19063-8. 2005
    The adapter SLP-76 is essential for T cell development and function. SLP-76 binds to the src homology 3 domain of Lck in vitro. This interaction depends on amino acids 185-194 of SLP-76...
  81. ncbi Tyrosine kinase p56lck regulates cell motility and nuclear factor kappaB-mediated secretion of urokinase type plasminogen activator through tyrosine phosphorylation of IkappaBalpha following hypoxia/reoxygenation
    Ganapati H Mahabeleshwar
    National Centre for Cell Science NCCS, NCCS Complex, Pune, Marahashtra 411 007, India
    J Biol Chem 278:52598-612. 2003
    ..The molecular mechanism(s) by which hypoxia/reoxygenation (H/R) regulates p56lck-dependent activation of NFkappaB through tyrosine phosphorylation of IkappaBalpha and modulates the expression of ..
  82. pmc Syk and ZAP-70 mediate recruitment of p56lck/CD4 to the activated T cell receptor/CD3/zeta complex
    M Thome
    Department of Immunology, Institut Pasteur, Paris, France
    J Exp Med 181:1997-2006. 1995
    ..suggested that the association of CD4 with TCR/CD3/zeta requires the interaction of the protein tyrosine kinase p56lck with CD4...
  83. ncbi The C terminus of T cell-specific adapter protein (TSAd) is necessary for TSAd-mediated inhibition of Lck activity
    Vibeke Sundvold-Gjerstad
    Institute of Basic Medical Sciences, Department of Anatomy, University of Oslo, Blindern, Oslo, Norway
    Eur J Immunol 35:1612-20. 2005
    ..Here, we show that human TSAd interacts with Lck through the Lck SH2 and SH3 domains and is a substrate for Lck...
  84. ncbi Role of Nef in HIV-1 replication and pathogenesis
    John L Foster
    Department of Internal Medicine, University of Texas Southwestern, Medical Center, Dallas, TX 75390, USA
    Adv Pharmacol 55:389-409. 2007
  85. ncbi Evidence of LAT as a dual substrate for Lck and Syk in T lymphocytes
    Yixing Jiang
    Department of Medicine and Pennstate Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033, United States
    Leuk Res 31:541-5. 2007
    ..In this study, we demonstrate that LAT serves as a dual substrate for both Lck and Syk kinases. LAT phosphorylation is absent in Lck-deficient J.CaM1...
  86. ncbi Residues Y429 and Y463 of the human CD5 are targeted by protein tyrosine kinases
    J M Vila
    Servei d Immunologia, Institut d Investigacions Biomediques August Pi i Sunyer IDIBAPS, Hospital Clinic, Barcelona, Spain
    Eur J Immunol 31:1191-8. 2001
    ..This is in agreement with data from direct in vitro kinase assays using purified recombinant Lck and Fyn protein tyrosine kinases...
  87. ncbi Molecular alterations of the Fyn-complex occur as late events of human T cell activation
    A Marie-Cardine
    Institute for Immunology, Immunomodulation Laboratory, Ruprecht Karls University of Heidelberg, Germany
    Eur J Immunol 29:1175-87. 1999
    ..the exception of pp85, these proteins seem to preferentially interact with Fyn since they are not detectable in Lck immunoprecipitates prepared under the same experimental conditions...
  88. pmc The SH3 domain of p56lck binds to proline-rich sequences in the cytoplasmic domain of CD2
    G M Bell
    Department of Medicine, Veterans Affairs Medical Center, San Francisco, California, USA
    J Exp Med 183:169-78. 1996
    ..An Src-like protein tyrosine kinase, p56lck, coprecipitates with CD2, and perturbation of CD2 by monoclonal antibodies results in an increase in the activity ..
  89. ncbi Regulation of protein kinase Ctheta function during T cell activation by Lck-mediated tyrosine phosphorylation
    Y Liu
    Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA
    J Biol Chem 275:3603-9. 2000
    ..CD3 activation. The Src family protein-tyrosine kinase, Lck, was critical in TCR-induced tyrosine phosphorylation of PKCtheta...
  90. ncbi Association between mitogen-activated protein kinase and the zeta chain of the T cell receptor (TcR) with the SH2,3 domain of p56lck. Differential regulation by TcR cross-linking
    A August
    Immunology Program, Sloan Kettering Institute for Cancer Research, New York, New York 10021, USA
    J Biol Chem 271:10054-9. 1996
    A number of protein-tyrosine kinases have been shown to be important in T cell activation. One such kinase, Lck, has been demonstrated genetically to be essential for T cell receptor (TcR) signaling, and the SH2 and SH3 (src homology 2 ..
  91. ncbi Modification of phosphatidylinositol 3-kinase SH2 domain binding properties by Abl- or Lck-mediated tyrosine phosphorylation at Tyr-688
    M von Willebrand
    Divisions of Cell Biology and Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA
    J Biol Chem 273:3994-4000. 1998
    ..We report that this phosphorylation event is readily catalyzed by the Abl and Lck protein-tyrosine kinases in vitro, by Bcr-Abl or a catalytically activated Lck-Y505F in co-transfected COS cells, ..
  92. ncbi A membrane proximal domain of the human interleukin-3 receptor beta c subunit that signals DNA synthesis in NIH 3T3 cells specifically binds a complex of Src and Janus family tyrosine kinases and phosphatidylinositol 3-kinase
    P Rao
    Holland Laboratory for BioMedical Science, American Red Cross, Rockville, Maryland 20855
    J Biol Chem 270:6886-93. 1995
    ..Purified Lyn and Lck kinase, but not Fes, could phosphorylate tyrosines in both domains...
  93. ncbi Regulation of Bcl-3 through interaction with the Lck tyrosine kinase
    Yujie Zhao
    Center for Advanced Biotechnology and Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA
    Biochem Biophys Res Commun 335:865-73. 2005
    ..that Bcl-3 interacts with the Fyn tyrosine kinase in platelets, we investigated possible interactions of Bcl-3 with Lck, a related tyrosine kinase important in lymphoid cells...
  94. ncbi The association of the protein tyrosine kinases p56lck and p60fyn with the glycosyl phosphatidylinositol-anchored proteins Thy-1 and CD48 in rat thymocytes is dependent on the state of cellular activation
    D Garnett
    MRC Cellular Immunology Unit, Sir William Dunn School of Pathology, University of Oxford, GB
    Eur J Immunol 23:2540-4. 1993
    ..are shown to be associated with multimolecular complexes of phosphoproteins including the protein tyrosine kinases p56lck and p60fyn in both rat and mouse thymocytes...
  95. pmc LCK-phosphorylated human killer cell-inhibitory receptors recruit and activate phosphatidylinositol 3-kinase
    F Marti
    The Immunology Program, Memorial Sloan Kettering Cancer Center, Cornell University Medical Center, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 95:11810-5. 1998
    ..Using these systems, we show that KIR CYT, once phosphorylated by the src-family tyrosine kinase LCK, additionally bind the p85alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase...
  96. ncbi Sequential involvement of Lck and SHP-1 with MHC-recognizing receptors on NK cells inhibits FcR-initiated tyrosine kinase activation
    B A Binstadt
    Department of Immunology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA
    Immunity 5:629-38. 1996
    ..Using a somatic genetic model, we first define a requirement for the Src family protein tyrosine kinase (PTK) Lck in mediating KIR tyrosine phosphorylation...
  97. pmc Activation of rabbit platelets by Ca2+ influx and thromboxane A2 release in an external Ca(2+)-dependent manner by zooxanthellatoxin-A, a novel polyol
    M C Rho
    Department of Pharmaceutical Molecular Biology, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
    Br J Pharmacol 115:433-40. 1995
    ..The resulting increase in [Ca2+]i subsequently stimulates the secondary release of TXA2 from platelets. Furthermore, the response to ZT-A may be associated with tyrosine phosphorylation...
  98. ncbi Detection of a physical and functional interaction between Csk and Lck which involves the SH2 domain of Csk and is mediated by autophosphorylation of Lck on tyrosine 394
    C Bougeret
    INSERM, , France
    J Biol Chem 271:7465-72. 1996
    ..analysis (BIAcore(TM)), we detected in vitro a specific interaction between Csk and one of its substrates Lck, a lymphocyte-specific member of the Src family...
  99. ncbi Signaling mechanisms of basic fibroblast growth factor in arterial cells from genetically hypertensive rat
    D L Zhu
    CNRS URA 1482, Laboratoire de Pharmacologie, , Paris, France
    Am J Hypertens 7:351-6. 1994
    ..Therefore, one may envisage that bFGF contributes, through paracrine/autocrine mechanisms, to the vascular smooth muscle hyperplasia/hypertrophy in SHR...
  100. ncbi Platelet-derived growth factor. Structure, function and implications in normal and malignant cell growth
    B Westermark
    Department of Pathology, University Hospital, Uppsala, Sweden
    Acta Oncol 32:101-5. 1993
    ..This view is supported by our recent finding that human melanoma cells that have been stably transfected with a PDGF B-chain cDNA, elicit a stroma response when transplanted to nude mice...
  101. ncbi Protein tyrosine kinase in colorectal adenoma
    T Hatada
    Department of Surgery, Hyogo College of Medicine, Japan
    Acta Oncol 32:23-8. 1993
    ....

Research Grants68

  1. Therapeutic targeting of Src kinase signal transduction pathways in AML
    Martin Carroll; Fiscal Year: 2013
    ..Interestingly, this analysis demonstrated phosphorylation of both lyn and lck tyrosine kinases in AML cells suggesting that Lyn and Lck, two members of the Src family kinases (SFKs) may ..
  2. The effects of hepatitis C virus (HCV) E2 protein on host immunomodulation
    Jack T Stapleton; Fiscal Year: 2013
    ..we hypothesize that E2 protein competes with the key proximal lymphocyte-specific protein tyrosine kinase (Lck) by serving as an alternative substrate for phosphorylation...
  3. Mechanism of CD40 signaling to APP metabolism
    Michael J Mullan; Fiscal Year: 2013
    ..We have identified CD40 signaling as a potentially key modulator of both amyloid and tau pathology and this proposal seeks to identify downstream molecules which are more tractable from a drug development perspective. ..
  4. Control of proximal T Cell Receptor signaling in tumor infiltrating lymphocytes.
    JEREMY CARLOS BURNS; Fiscal Year: 2013
    ..Receptor (TCR) signal transduction, which our lab has previously shown to result from functional inhibition of p56lck kinase...
  5. Copolymer hydrogel microspheres for analysis of kinase activity in cell lysates
    Sean P Palecek; Fiscal Year: 2010
    ..This assay will likely be more rapid and less expensive than current methods, and have the advantage of predicting response to drug treatment. ..
  6. SOCS: Its Regulation and Role in Oncogenesis
    Chao Lan Yu; Fiscal Year: 2010
    ..Our preliminary studies find that cells transformed by Lck exhibit active STATS but fail to express both SOCS genes...
  7. STRUCTURAL STUDIES OF A T CELL SPECIFIC TYROSINE KINASE
    Amy H Andreotti; Fiscal Year: 2013
    ..The Src kinase, Lck, activates Itk following TCR engagement by phosphorylating a specific tyrosine in the Itk kinase domain and we have ..
  8. An allosteric inhibitor of ZAP-70 as a novel therapeutic for autoimmune disease
    Arthur Weiss; Fiscal Year: 2010
    ..Once associated with the ITAMS, ZAP-70 is activated by its phosphorylation by the Src kinase Lck and by its own trans- autophosphorylation...
  9. STRUCTURAL STUDY OF THE INSULIN RECEPTOR TYROSINE KINASE
    Stevan R Hubbard; Fiscal Year: 2010
    ..By understanding at the molecular level how the insulin receptor is regulated, we hope to facilitate efforts to design small-molecule agonists and inhibitors that could potentially be used as anti-diabetic therapeutics. ..
  10. NMR STRUCTURE OF PEPTIDE AND PROTEIN COMPLEXES
    Carol B Post; Fiscal Year: 2013
    ..The proposed research aims to elucidate mechanisms of this control for Syk and Src PTKs with the goal of contributing new knowledge that is useful in fighting human disease. ..
  11. Phosphoproteomic Analysis of T Cell Activation Pathways
    ARTHUR ROBERT SALOMON; Fiscal Year: 2013
    ..within the pathway through quantitative phosphoproteomic analysis of T cells with disrupted pathway proteins LCK, PLCy1, VAV, and ERK...
  12. Interferon-gamma limits the effectiveness of peptide vaccines for cancer
    Esteban Celis; Fiscal Year: 2013
    ..tumor cells prevents the full activation of the T cells by reducing the ability of the CD8 molecules to recruit the Lck lymphocyte-specific tyrosine kinase into the immunological synapse...
  13. Src Family Kinases as Molecular Targets for HIV/Nef
    THOMAS EDWARD SMITHGALL; Fiscal Year: 2010
    ..Our work is focused on the interaction of Nef with protein kinases in infected cells. Completion of these experiments will validate these Nef-kinase complexes as targets for the discovery of new anti-HIV therapeutics. ..
  14. Complexes of HIV-1 Nef with Src-family Kinases as Therapeutic Targets
    Lori A Emert Sedlak; Fiscal Year: 2010
    ..This compound represents the first to target a viral protein:host cell protein kinase complex, providing a new lead for anti-HIV drug development. ..
  15. Genetic and Immunological Impact of the HRES-1/Rab4 Locus in SLE
    Andras Perl; Fiscal Year: 2013
    ..The key intracellular transducer of T-cell activation, Lck, is brought to the IS via binding to CD4. TCR6 chain binds to the TFR...
  16. Regulation of ITK in Lung Allergy
    Constantine D Tsoukas; Fiscal Year: 2010
    ..activation of ITK requires the presence of the adaptor protein SLP 76 and transphosphorylation by the Src kinase LCK. In the absence of SLP 76 ITK does not become transphosphorylated and thus remains enzymatically inactive...
  17. SLAT: A novel GEF coordinating actin remodeling and Ca2+ signaling in T cells
    Amnon Altman; Fiscal Year: 2013
    ..Our work also revealed that antigen-induced translocation of SLAT to the immunological synapse (IS) is mediated by Lck kinase-dependent phosphorylation of a SLAT ITAM-like motif, and that the Ca2+/NFAT regulatory activity of SLAT ..
  18. Biochemical and Spatial Regulation of IKKg/NEMO During T Cell Activation
    Lawrence P Kane; Fiscal Year: 2013
    ..Thus, in Aim 1, we will determine the role of Zap70 and Lck in recruitment of the IKK complex to TCR microclusters...
  19. The role of RIAM in T cell immunity and tolerance
    Vassiliki A Boussiotis; Fiscal Year: 2013
    ..RIAM also interacts with Gads and undergoes Lck-mediated phosphorylation in its PH domain...
  20. Intermolecular Interactions in the Immunological Synapse
    Karsten Sauer; Fiscal Year: 2013
    ..e. the adhesion function of CD8) versus its importance in concentrating the kinase Lck, will be measured...
  21. Structural Determinants of TCR Assembly and Signaling
    Kai W Wucherpfennig; Fiscal Year: 2013
    ..This means that the ITAM has to dissociate from the membrane before it can be phosphorylated by Lck. The absence of an alpha-helical periodicity of these protein-lipid interactions further suggests that the actual ..
  22. Spatial coordination of CD28 and TCR signaling
    LANCE C KAM; Fiscal Year: 2013
    ..We focus specifically on PKC8 and Lck as two recognized molecules at the junction of these pathways, and seek to define how the biophysical behaviors of ..
  23. T cell regulation by N-glycosylation
    Michael Demetriou; Fiscal Year: 2013
    ..This in turn blocks recruitment of Nck, WASp, SLP-76 and CD4-Lck to TCR, F-actin remodeling and transfer of the complex to GM1/cholesterol-enriched microdomains (GEMs)...
  24. CAML in T cell Development and Function
    Richard J Bram; Fiscal Year: 2011
    ..We have also discovered that CAML interacts with p56Lck, a protein kinase with established roles in T cell development, proliferation, and activation-induced apoptosis, ..
  25. REQUIREMENT FOR SENSITIVE T CELL RESPONSE TO ANTIGEN
    MICHAEL LORAN DUSTIN; Fiscal Year: 2013
    ..In Aim 2 we will test the importance of different putative interactions of CCM with MHC class II, Lck, membrane domains, the TCR and itself in T cell sensitivity to antigen...
  26. Mechanisms of H. pylori-Induced Hypochlorhydria
    Adam J Smolka; Fiscal Year: 2010
    ..Improved mechanistic understanding of H. pylori pathophysiology will inform later studies in translational models and in humans. ..
  27. Modulation of T cell Homeostasis in Myelodysplastic Syndrome (MDS)
    Javier Pinilla; Fiscal Year: 2012
    ..Mechanistic studies will aide our understanding of T-cell immunity and improve our ability to utilize this form of immunotherapy and other forms for the treatment of cancer in general. ..
  28. c-Abl-mediated Suppression of Breast Cancer Development and Metastasis
    WILLIAM SCHIEMANN; Fiscal Year: 2013
    ..g., c-Abl for docetaxel response) and treatment options (e.g., Securinine and DPH) for TNBCs. ..
  29. Syk blockade in bullous skin diseases
    Uma Sinha; Fiscal Year: 2012
    ..In this Phase I program we will provide proof-of-concept for Syk inhibitors in BP using both animal models and relevant ex vivo human biospecimens. ..
  30. Focal Adhesion Kinase - Tumor Biology and Therapeutics
    William G Cance; Fiscal Year: 2013
    ..Thus, this application will provide novel molecular cancer therapeutics that target the focal adhesion kinase. ..
  31. Proximity between immune receptors on the cell surface and the sensitivity of Tce
    Yuri Sykulev; Fiscal Year: 2010
    ..provided by applicant): Several lines of evidence, including our own data, suggest that a fraction of CD8, p56lck- associated protein that marks a population of cytotoxic T lymphocytes (CTL) and binds to the nonpolymorphic ..
  32. CELL SURFACE RECOGNITION AND CELL INTERACTIONS
    William J Snell; Fiscal Year: 2012
    ..Studying flagellar adhesion and flagellar shortening in Chlamydomonas will continue to uncover novel and fundamental properties of these remarkable organelles. ..
  33. Mechanisms of Breast Tumor Cell Growth, Motility, and Antiestrogen Response
    Amy H Bouton; Fiscal Year: 2013
    ..abstract_text> ..
  34. The role of BMX in Lymphangiogenesis
    Dennis Jones; Fiscal Year: 2011
    ..Ultimately novel inhibitor molecules against Bmx may be effective in cancer therapy. ..
  35. Immune Receptors on Cytotoxic Lymphocytes and Target Cells
    Yuri Sykulev; Fiscal Year: 2012
    ..These CD4 clusters sustain activation of Lck suggesting a possible synergy with TCR clusters that facilitates focusing of cytolytic granules in the secretory ..
  36. Mechanisms of Overexpressed TrkB in Inducing Pancreatic Cancer Metastasis
    Paul J Chiao; Fiscal Year: 2013
    ..Targeting specific mutations and signaling pathways in pancreatic cancer may be one of the novel therapeutic interventions to treat cancer metastasis. ..
  37. Novel Small Molecule Inhibitor of Rheumatoid Arthritis
    Jun Hayashi; Fiscal Year: 2009
    b>Lck is a Src family non-receptor tyrosine kinase expressed by T lineage lymphocytes. In T cells, Lck plays an essential role in the generation of antigen-mediated activation signals...
  38. A Tumor Suppressor Function for the c-Fes Tyrosine Kinase in Colon Cancer
    THOMAS EDWARD SMITHGALL; Fiscal Year: 2012
    ..If c-fes is a true tumor suppressor, then mice lacking c-fes function are expected to develop more severe disease in terms of tumor size, number, and invasiveness. ..
  39. MerTK regulation of the PTTG and RPE phagocytosis
    Qingxian Lu; Fiscal Year: 2012
    ..The data from these studies is expected to provide us the new knowledge and understanding of the RPE function, which will allow us to develop and implement new therapies for treatment of RP caused by RPE dysfunction. ..
  40. Dissecting Wnt/PCP Signaling in Developing Cochlear Sensory Epithelium
    Xiaowei Lu; Fiscal Year: 2012
    ....
  41. Small Molecule Inhibitors of ZAP-70 for the Treatment of Autoimmune Disorders
    Mark Gallop; Fiscal Year: 2013
    ....
  42. Negative regulation of TCR-associated PTKs
    ROBERT RICKERT; Fiscal Year: 2007
    ..We will determine to what extent TCR signaling is altered in the absence of PEP and if Lck and Fyn are hyperactive...
  43. Methodology for Identification of Substrate-Competitive Kinase Inhibitors
    Matthew B Soellner; Fiscal Year: 2012
    ..Our methodology will initially focus on two kinases involved in cancer (c-Abl and c-Src) and two kinases involved in African sleeping sickness. ..
  44. Molecular Basis of Pathogenicity of IgA1-containing Immune Complexes
    Jan Novak; Fiscal Year: 2012
    ..Relevance: The improved understanding of the pathogenesis of IgAN will identify therapeutic targets for disease-specific therapy of IgAN as well as potential prognostic biomarkers. ..
  45. Recent Thymic Emigrants of the CD4 T-cell Lineage
    DAVID BRAM LEWIS; Fiscal Year: 2013
    ....
  46. ANTIBODY V GENE EXPRESSION B CELL LYMPHOCYTIC LEUKEMIA
    Thomas J Kipps; Fiscal Year: 2013
    ..Further studies could enable us to refine this approach toward development of truly effective immune therapy for patients with this disease. ..
  47. Role of Src Kinases in T Cell Receptor Signaling
    David Straus; Fiscal Year: 2004
    ..We will take advantage of our ability to express mutants of the Src-family kinase Lck in an Lck-deficient T cell line to determine what steps in the activation process are dependent upon particular ..
  48. Pathogenic Role of Islet Cell Autoantibodies in Type I Diabetes
    Raphael A Clynes; Fiscal Year: 2011
    ..abstract_text> ..
  49. METALLOPROTEINASES IN TUMOR NEOVASCULARIZATION
    Alex Y Strongin; Fiscal Year: 2013
    ..Precise analysis of the MT1-MMP functionality will pave the way for rational design of inhibitory molecules directed against its specific enzymatic and non-enzymatic functions. ..
  50. Regulation of breast cancer progression by FAK expression in tumor macrophages
    J Thomas Parsons; Fiscal Year: 2010
    ..It is anticipated that, through the knowledge gained from these studies, there will be a significant reduction in mortality from breast cancer. ..
  51. Recent Thymic Emigrants of the CD4 T-cell Lineage
    David Lewis; Fiscal Year: 2009
    ..Together, these studies will substantially enhance our understanding of the role of thymic RTE production in maintaining the peripheral na[unreadable]ve CD4 T-cell compartment in health and disease. ..
  52. Functions of Protein Tyrosine Kinase 6 in the Gastrointestinal Tract
    Angela L Tyner; Fiscal Year: 2013
    ..Colon cancer becomes deadly after it metastasizes. Understanding the functions of PTK6 in the normal colon and in colon cancer initiation and progression will be critical for evaluating its potential as a therapeuic target. ..
  53. Mechanisms of Kinase Function and Drug Resistance in Cancer
    Karsten Sauer; Fiscal Year: 2013
    ..This will aid the development of more selective, less side-effect and less drug-resistance prone therapeutics. ..
  54. Thymocyte tuning after selection: mechanisms to avoid autoreactivity
    Terri M Laufer; Fiscal Year: 2010
    ..makes T cell activation more dependent on engagement of CD4 by increasing the allegiance of the tyrosine kinase, Lck, for CD4...
  55. Src inhibition in Colorectal Cancer
    Scott Kopetz; Fiscal Year: 2012
    ..Successful implementation will improve the effectiveness of current chemotherapies for metastatic colorectal cancer, resulting in improved outcomes for the metastatic colorectal cancer population. ..
  56. ZAP-70 Deficiency: A model for gene therapy studies
    Naomi Taylor; Fiscal Year: 2010
    ..Altogether, the data emerging from these experiments should promote the development of an optimal and safe gene therapy strategy for patients with ZAP-70-deficiency as well as other forms of SCID. ..
  57. Tumor and PTK-Targeted Therapy by FUS1 and PTK inhibitor
    Lin Ji; Fiscal Year: 2010
    ....
  58. Type 1 Diabetes TrialNet: Clinical Center at Berrie Center, Columbia University
    Robin S Goland; Fiscal Year: 2013
    ..As a key component of this TrialNet application, we propose an intervention study to investigate its efficacy in human subjects with new-onset T1DM (onset within 100 days of randomization). ..
  59. SYNTHETIC REGULATORS OF TYROSINE PROTEIN KINASES
    David S Lawrence; Fiscal Year: 2013
    ..A new breed of imaging reagents, with properties that display a high degree of spatial (and temporal) resolution, will be prepared to address this unexpected change in direction of cancer research. ..
  60. Role of PTPRkappa in Lck Regulation During T cell Development
    JANE CHERIE YACIUK; Fiscal Year: 2010
    ..development of CD4 T cells in LEC rats, plays a central role in CD4 lineage commitment through modulation of Lck kinase activity. To test this hypothesis, aims include to: 1...
  61. HIV protection by ZFN-based disruption of CCR5 gene in Hematopoietic stem cells
    Haoquan Wu; Fiscal Year: 2013
    ....
  62. Tumor-Induced Defective CTL Lytic Function
    Alan B Frey; Fiscal Year: 2010
    ..signaling defect is proximal: contact with tumor causes rapid dephosphorylation of the activation motif (Y394) in p56lck therein preventing propagation of the activating signal...
  63. p56lck Inhibitors as Potential Immunosuppressive Drugs.
    ALEXANDER MACKERELL; Fiscal Year: 2004
    SH2 domains in non-receptor tyrosine kinases, such as p56lck, represent molecular targets that are central to cellular signaling pathways related to immune response...
  64. C-FES PROTEIN-TYROSINE KINASE IN MYELOID DIFFERENTIATION
    Robert Glazer; Fiscal Year: 1993
    ..Cognizance of this regulatory process should aid in the design of differentiation- specific therapies for myeloid leukemias...
  65. INTERFERON SIGNAL TRANSDUCTION IN T CELLS
    Andrew Larner; Fiscal Year: 2001
    ..a rapid association with the alpha chain of the IFNalpha receptor (IFNalphaR1) of the protein tyrosine kinases Lck and ZAP-70 and the protein tyrosine phosphatase, CD-45...
  66. OSTEOCLASTIC PHOSPHOTYROSYL PHOSPHATASE AND RESORPTION
    KIN HING LAU; Fiscal Year: 2002
    ....
  67. PROTEIN TYROSINE KINASE TYRO-3
    ANNE PRIETO; Fiscal Year: 2003
    ..Through these efforts we hope to uncover the role of Tyro-3 in molecular mechanisms of cell adhesion, intracellular signaling and neuroplasticity in the normal and diseases nervous system. ..
  68. REGULATION OF BCR MEDIATED SIGNAL TRANSDUCTION BY CD45
    LOUIS JUSTEMENT; Fiscal Year: 2002
    ..Thus, the studies proposed above may provide information that enhances our understanding of the events which result in aberrant activation of the B cell. ..