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| LckSummaryGene Symbol: Lck Description: lymphocyte-specific protein tyrosine kinase Alias: LSK, YT16, p56lck, pp58lck, T-lymphocyte specific protein tyrosine kinase p56lck, leukocyte C-terminal Src kinase, lymphocyte cell-specific protein-tyrosine kinase, p56(LSTRA) protein-tyrosine kinase, proto-oncogene tyrosine-protein kinase LCK, t cell-specific protein-tyrosine kinase, tyrosine-protein kinase Lck Species: human Top Publications
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Function of the Src-family kinases, Lck and Fyn, in T-cell development and activationEmil 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. 2004The function of the Src-family kinases (SFKs) Lck and Fyn in T cells has been intensively studied over the past 15 years...
SHP2-interacting transmembrane adaptor protein (SIT), a novel disulfide-linked dimer regulating human T cell activationA 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...
Specific dephosphorylation of the Lck tyrosine protein kinase at Tyr-394 by the SHP-1 protein-tyrosine phosphataseG 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...
A weak Lck tail bite is necessary for Lck function in T cell antigen receptor signalingKonstantina 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 ..
Constitutively active Lck kinase in T cells drives antigen receptor signal transductionKonstantina 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 ..
Human homologue of the Drosophila discs large tumor suppressor binds to p56lck tyrosine kinase and Shaker type Kv1.3 potassium channel in T lymphocytesT 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...
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 activationN 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...
Lck phosphorylates the activation loop tyrosine of the Itk kinase domain and activates Itk kinase activityS 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 ..
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-kinaseK 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...
Regulation of Fyn through translocation of activated Lck into lipid raftsDominik 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. 2003Whether or how the activation of Lck and Fyn during T cell receptor (TCR) signaling is coordinated, and their delivery of function integrated, is unknown...
Structural basis for activation of human lymphocyte kinase Lck upon tyrosine phosphorylationH Yamaguchi
Department of Biochemistry and Molecular Biophysics, Columbia University, New York 10032, USA
Nature 384:484-9. 1996Regulation through phosphorylation is a characteristic of signalling pathways and the lymphocyte kinase Lck (p56lck) both performs phosphorylation and is affected by it...
Identification of preferred protein interactions by phage-display of the human Src homology-3 proteomeSatu Kärkkäinen
Institute of Medical Technology, University of Tampere and Tampere University Hospital, Biokatu 8, Tampere 33014, Finland
EMBO Rep 7:186-91. 2006....
The SH3 domain of p56lck binds to proline-rich sequences in the cytoplasmic domain of CD2G 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 ..
Cutting edge: the CD45 tyrosine phosphatase is an inhibitor of Lck activity in thymocytesU D'Oro
Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 162:1879-83. 1999A 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)...
Genetically encoded Förster resonance energy transfer sensors for the conformation of the Src family kinase LckWolfgang Paster
Department of Molecular Immunology, Center for Physiology, Pathophysiology and Immunology, Medical University of Vienna, Vienna, Austria
J Immunol 182:2160-7. 2009The 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...
Activation of phosphatidylinositol-3-kinase in Jurkat T cells depends on the presence of the p56lck tyrosine kinaseM 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...
Regulation of the Src family kinase Lck by Hsp90 and ubiquitinationAna Giannini
Department of Immunobiology, Guy s Hospital, King s College London, United Kingdom
Mol Cell Biol 24:5667-76. 2004Regulation 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...
Lck is required for stromal cell-derived factor 1 alpha (CXCL12)-induced lymphoid cell chemotaxisMarit 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...
Proline residues in CD28 and the Src homology (SH)3 domain of Lck are required for T cell costimulationA 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. 1999The 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...
Identification of two SH3-binding motifs in the regulatory subunit of phosphatidylinositol 3-kinaseR 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...
Unc119, a novel activator of Lck/Fyn, is essential for T cell activationMagdalena 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. 2004The 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...
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 cellsPanagiotis 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. 2003In 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...
Profound block in thymocyte development in mice lacking p56lckT J Molina
Ontario Cancer Institute, University of Toronto, Canada
Nature 357:161-4. 1992The 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...
A 10-aa-long sequence in SLP-76 upstream of the Gads binding site is essential for T cell development and functionLalit 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. 2005The 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...
Syk and ZAP-70 mediate recruitment of p56lck/CD4 to the activated T cell receptor/CD3/zeta complexM 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...
Binding of HIV-1 to its receptor induces tyrosine phosphorylation of several CD4-associated proteins, including the phosphatidylinositol 3-kinaseG 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...
Modulation of Lck function through multisite docking to T cell-specific adapter proteinStine 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. 2008T cell-specific adapter protein (TSAd), encoded by the SH2D2A gene, interacts with Lck through its C terminus and thus modulates Lck activity...
SHP-1 regulates Lck-induced phosphatidylinositol 3-kinase phosphorylation and activityB 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. 1999Ligation of the T cell antigen receptor (TCR) activates the Src family tyrosine kinase p56 Lck, which, in turn, phosphorylates a variety of intracellular substrates...
Lad, an adapter protein interacting with the SH2 domain of p56lck, is required for T cell activationY B Choi
Signal Transduction Laboratory Mogam Biotechnology Research Institute, Koosungmyon, Yonginsi, Kyunggido, Korea
J Immunol 163:5242-9. 1999T cell-specific Src family tyrosine kinase, p56lck, plays crucial roles in T cell differentiation, activation, and proliferation...
Dok-3, a novel adapter molecule involved in the negative regulation of immunoreceptor signalingS Lemay
McGill Cancer Centre, McGill University, Montreal, Quebec, Canada H3G 1Y6
Mol Cell Biol 20:2743-54. 2000....
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 activationT 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...
Evidence of LAT as a dual substrate for Lck and Syk in T lymphocytesYixing 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...
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 membraneE 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...
LCK-phosphorylated human killer cell-inhibitory receptors recruit and activate phosphatidylinositol 3-kinaseF 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...
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 activationD 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...
Molecular cloning of SKAP55, a novel protein that associates with the protein tyrosine kinase p59fyn in human T-lymphocytesA 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 ..
Modification of phosphatidylinositol 3-kinase SH2 domain binding properties by Abl- or Lck-mediated tyrosine phosphorylation at Tyr-688M 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, ..
Regulation of Bcl-3 through interaction with the Lck tyrosine kinaseYujie 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...
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-kinaseP 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...
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-linkingA August
Immunology Program, Sloan Kettering Institute for Cancer Research, New York, New York 10021, USA
J Biol Chem 271:10054-9. 1996A 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 ..
Sequential involvement of Lck and SHP-1 with MHC-recognizing receptors on NK cells inhibits FcR-initiated tyrosine kinase activationB 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...
Activation of rabbit platelets by Ca2+ influx and thromboxane A2 release in an external Ca(2+)-dependent manner by zooxanthellatoxin-A, a novel polyolM 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...
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 394C 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...
Signaling mechanisms of basic fibroblast growth factor in arterial cells from genetically hypertensive ratD 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...
Platelet-derived growth factor. Structure, function and implications in normal and malignant cell growthB 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...
Protein tyrosine kinase in colorectal adenomaT Hatada
Department of Surgery, Hyogo College of Medicine, Japan
Acta Oncol 32:23-8. 1993....
Protein tyrosine kinase activity in human thyroid papillary carcinomaY Yasuda
Second Department of Surgery, Hyogo College of Medicine, Japan
Acta Oncol 31:409-12. 1992..These findings indicate that elevated cytosolic PTK activity may be a potentially useful marker for papillary thyroid carcinoma...
Activation of p58c-fgr and p53/56lyn in adherent human neutrophils: evidence for a role of divalent cations in regulating neutrophil adhesion and protein tyrosine kinase activitiesS R Yan
Institute of General Pathology, University of Verona, Italy
J Inflamm 45:297-311. 1995....
Effect of hypoxia on protein tyrosine kinase activity in cortical membranes of newborn piglets--the role of nitric oxideOm Prakash Mishra
Department of Pediatrics, Neonatal Research Laboratory, Drexel University College of Medicine, MCP, Room 701, 7th Floor Heritage Building, 3300 Henry Avenue, Philadelphia, PA 19129, USA
Neurosci Lett 372:114-8. 2004..We propose that the hypoxia-induced increase in protein tyrosine kinase activity leading to increased phosphorylation of Bcl-2 is a critical link to hypoxic neuronal injury pathway...
Demonstration of selective protein kinase C-dependent activation of Src and Lck tyrosine kinases during ischemic preconditioning in conscious rabbitsP Ping
Experimental Research Laboratory, Division of Cardiology and the Department of Physiology and Biophysics, University of Louisville and Jewish Hospital Heart and Lung Institute, KY 40202, USA
Circ Res 85:542-50. 1999..and 4-minute reperfusion) induces selective activation of 2 members of the Src family of tyrosine kinases, Src and Lck, in the heart of conscious rabbits...
L-selectin activates the Ras pathway via the tyrosine kinase p56lckB Brenner
Department of Pediatrics, University of Heidelberg, Germany
Proc Natl Acad Sci U S A 93:15376-81. 1996..of Jurkat cells using different antibodies or glycomimetics resulted in activation of the src-tyrosine kinase p56lck; tyrosine phosphorylation of intracellular proteins, in particular mitogen-activating protein kinase and L-..
Effects of the novel and potent lymphocyte-specific protein tyrosine kinase inhibitor TKM0150 on mixed lymphocyte reaction and contact hypersensitivity in miceTetsuo Takayama
Medicinal Research Laboratories, Taisho Pharmaceutical Co, Ltd, Saitama, Japan
Arzneimittelforschung 60:282-5. 2010Lymphocyte-specific protein tyrosine kinase (Lck) plays a critical role in T cell activation...
Calcium-induced ERK activation in human T lymphocytes occurs via p56(Lck) and CaM-kinaseR A Franklin
Department of Microbiology and Immunology, East Carolina University School of Medicine, Brody Building, Greenville, NC 27858, USA
Mol Immunol 37:675-83. 2000..of T lymphocytes with ionomycin or A23187 resulted in a CaM-kinase-dependent shift in the mobility of p56(Lck)...
Properties of tripartite chimeras between Src and LckA Kashishian
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104
Oncogene 5:1463-70. 1990..domains of Src-family kinases, we have assembled five chimeric molecules containing parts of p60c-src (Src) and p56lck (Lck)...
Differential effects of expression of the CD45 tyrosine protein phosphatase on the tyrosine phosphorylation of the lck, fyn, and c-src tyrosine protein kinasesT R Hurley
Molecular Biology and Virology Laboratory, Salk Institute, San Diego, California 92186
Mol Cell Biol 13:1651-6. 1993..We have studied the phosphorylation of the closely related lck, fyn, and c-src tyrosine protein kinases in leukemic murine T-cell lines that have lost the expression of CD45...
Partial purification and characterization of the lck protein-tyrosine kinase from bovine thymusQ M Wang
Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy, Purdue University, West Lafayette, IN 47907
Biochem J 279:567-74. 1991..were also recognized by polyclonal anti-peptide antibodies raised against the C-terminal 33 amino acids of p56lck, a major T lymphocyte protein-tyrosine kinase...
Zap70 signaling pathway mediates glucocorticoid receptor-dependent transcriptional activation: role in the regulation of annexin 1 expression in T cellsMohammad Ishaq
Laboratory of Molecular Cell Biology, SAIC Frederick, National Cancer Institute, Frederick, MD 21702, USA
J Immunol 179:3851-8. 2007..b>Lck-lacking Jurkat cells were also found to show markedly reduced GR activation, and reconstitution with Lck restored ..
Neocortical neurons lacking the protein-tyrosine kinase B receptor display abnormal differentiation and process elongation in vitro and in vivoM A Gates
Division of Neuroscience, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
Neuroscience 98:437-47. 2000....
Regulation of eicosanoid biosynthesis in the macrophage. Involvement of protein tyrosine phosphorylation and modulation by selective protein tyrosine kinase inhibitorsK B Glaser
Division of Immunopharmacology, Wyeth Ayerst Research, Princeton, NJ 08543 8000
Biochem Pharmacol 45:711-21. 1993..The use of selective PTK inhibitors suggests a common role for PTK and tyrosine phosphorylation in eicosanoid biosynthesis in the murine peritoneal macrophage...
Differential regulation of fyn-associated protein tyrosine kinase activity by macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF)Y Li
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201
J Leukoc Biol 57:484-90. 1995..Collectively, our data suggest that the activation of fyn kinase is closely associated with the acquisition of adherent capacity in maturing macrophages...
Differential regulation of T cell receptor-mediated Th1 cell IFN-gamma production and proliferation by divergent cAMP-mediated redox pathwaysR Cochrane
Department of Pathology, The University of Connecticut Health Center, Farmington, CT 06030 3105, USA
J Interferon Cytokine Res 21:797-807. 2001..Immunoblotting of lysates from an FSK-treated Th1 clone with antibodies to a carboxy-terminal epitope of p56(lck), a signal transduction enzyme upstream from ERK-1 and ERK2, did not detect p56(lck) unless the lysates were ..
Transcriptional activation of lck by retrovirus promoter insertion between two lymphoid-specific promotersH T Adler
Molecular Biology and Virology Laboratory, Salk Institute, San Diego, California 92138
J Virol 62:4113-22. 1988b>p56lck, a member of the src family of cytoplasmic tyrosine protein kinases, is expressed primarily in lymphoid cells...
Increased ubiquitination and reduced expression of LCK in T lymphocytes from patients with systemic lupus erythematosusElizabeth C Jury
Royal Free and University College Medical School, University College, London, UK
Arthritis Rheum 48:1343-54. 2003..To explore regulation of proximal signaling and composition of lipid rafts in T lymphocytes from patients with systemic lupus erythematosus (SLE)...
Association of herpesvirus saimiri tip with lipid raft is essential for downregulation of T-cell receptor and CD4 coreceptorNam Hyuk Cho
Department of Microbiology and Molecular Genetics and Tumor Virology Division, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772 9102, USA
J Virol 80:108-18. 2006..HVS), which is a T-lymphotropic tumor virus, is constitutively targeted to lipid rafts and interacts with cellular Lck tyrosine kinase and p80 WD repeat-containing endosomal protein...
The cytoplasmic domain of CD4 is sufficient for its down-regulation from the cell surface by human immunodeficiency virus type 1 NefS J Anderson
Department of Virology and Molecular Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38101
J Virol 68:3092-101. 1994..Since the cytoplasmic domain of CD4 is also the site of its association with p56lck, we used a series of CD4 mutants to determine whether the regions of the cytoplasmic domain of CD4 required for ..
Human airway epithelial cells stimulate T-lymphocyte lck and fyn tyrosine kinaseT H Kalb
Department of Medicine, Mt Sinai Medical Center, New York, New York 10029, USA
Am J Respir Cell Mol Biol 17:561-70. 1997..To determine whether CD3 associated p59fyn, or CD4 and CD8 associated p56lck phosphotyrosine kinases (PTK) were involved, we assayed kinase activity in lymphocyte lysates immunoprecipitated ..
The reproductive activity in the testis of Podarcis s. sicula involves D-aspartic acid: a study on c-kit receptor protein, tyrosine kinase activity and PCNA protein during annual sexual cycleFranca Raucci
Department of Life Sciences, Second University of Naples, Via Vivaldi 43, 81100 Caserta, Italy
Gen Comp Endocrinol 161:373-83. 2009..sicula, suggesting that a sequential cascade of a functional relationship between testosterone levels, c-kit receptor protein, tyrosine kinase activity and PCNA could be partly mediated by D-aspartic acid...
Effects of magnesium sulfate administration during hypoxia on CaM kinase IV and protein tyrosine kinase activities in the cerebral cortex of newborn pigletsAhmed G Mami
Department of Pediatric Surgery, Drexel University College of Medicine and St Christopher s Hospital for Children, Philadelphia, PA 19129, USA
Neurochem Res 31:57-62. 2006..As a result, phosphorylation of CREB and Bcl-2 family of proteins is prevented leading to prevention of programmed cell death...
JAK3 protein tyrosine kinase mediates interleukin-7-induced activation of phosphatidylinositol-3' kinaseN Sharfe
Division of Immunology and Allergy, Hospital for Sick Children, University of Toronto, Ontario, Canada
Blood 86:2077-85. 1995..IL-7-induced activation of three cyoplasmic tyrosine kinases in T cells, Jak1, Jak3, and the src-like kinase p56lck. Many members of the cytokine receptor superfamily activate the Jak protein tyrosine kinase family, with resultant ..
Selective inhibition of the platelet-derived growth factor signal transduction pathway by a protein-tyrosine kinase inhibitor of the 2-phenylaminopyrimidine classE Buchdunger
CIBA Pharmaceuticals Division, Oncology Research Department, Ciba Geigy Limited, Basel, Switzerland
Proc Natl Acad Sci U S A 92:2558-62. 1995..These findings suggest that CGP 53716 may have therapeutic potential for the treatment of diseases involving abnormal cellular proliferation induced by PDGF receptor activation...
Association between Lyn protein tyrosine kinase (p53/56lyn) and the beta subunit of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors in a GM-CSF-dependent human megakaryocytic leukemia cell line (M-07e)Y Li
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA
J Immunol 155:2165-74. 1995....
Protein tyrosine kinase-dependent release of intracellular calcium in the sea urchin eggS S Shen
Department of Zoology and Genetics, Iowa State University, Ames 50011 3223, USA
Dev Growth Differ 41:345-55. 1999..Therefore, it was concluded that sea urchin eggs contain a PTK-dependent pathway that can mediate intracellular Ca2+ release, but PTK activity does not appear to be required for the fertilization response...
Two lck transcripts containing different 5' untranslated regions are present in T cellsA F Voronova
Molecular Biology and Virology Laboratory, Salk Institute, San Diego, California 92138
Mol Cell Biol 7:4407-13. 1987b>p56lck is a new member of the src family of cellular tyrosine protein kinases...
The structure-activity relationship of the series of non-peptide small antagonists for p56lck SH2 domainSee Hyoung Park
Signal Transduction Laboratory, Mogam Biotechnology Research Institute, 341 Pojung Ri, Koosung Myun, Yongin City, Kyunggi Do, 449 910, Republic of Korea
Bioorg Med Chem 15:3938-50. 2007..acid (alpha-o-caffeoyl-3,4-dihydroxyphenyl-lactic acid; RosA) from Prunella vulgaris as an antagonist for the p56lck SH2 domain by screening natural products...
Interleukin 2 regulates the activity of the lyn protein-tyrosine kinase in a B-cell lineT Torigoe
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104 6082
Proc Natl Acad Sci U S A 89:2674-8. 1992Recently, interleukin 2 (IL-2) has been shown to induce increased activity of the p56lck protein-tyrosine kinase (PTK) in T-cell and natural killer cell lines, and evidence for a direct interaction between the p75 subunit of the IL-2 ..
Signal transducer and activator of transcription 5b: a new target of breast tumor kinase/protein tyrosine kinase 6Amanda M Weaver
Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA
Breast Cancer Res 9:R79. 2007..Only a few substrates of the Brk tyrosine kinase have been identified, the most recent being STAT3. In the present article we investigate the potential role of Brk in the phosphorylation and activation STAT5b...
[Effects of matrine on the activity of protein tyrosine kinase and phosphatase in K562 cells]Bei Zhong Liu
Department of Clinical Biochemistry, Chongqing Medical University, Chongqing 400016, P R China
Ai Zheng 21:1292-5. 2002..The differentiation of K562 cells can be induced by a given concentration of matrine. This study was designed to investigate the mechanism of signal transduction in induced differentiation of K562 cells...
Protein-tyrosine kinase CAKbeta/PYK2 is activated by binding Ca2+/calmodulin to FERM F2 alpha2 helix and thus forming its dimerTakayuki Kohno
The Department of Biochemistry, Cancer Research Institute, Sapporo Medical University School of Medicine, South 1, West 17, Chuo Ku, Sapporo 060 8556, Japan
Biochem J 410:513-23. 2008..Our results indicate that Ca2+/calmodulin binding to the FERM F2-alpha2 helix of CAKbeta/PYK2 releases its kinase domain from autoinhibition by forming a dimer...
The protein tyrosine kinase p56lck regulates TCR expression and T cell selectionP O Ericsson
Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada
Int Immunol 7:617-24. 1995The role of the protein tyrosine kinase (PTK), p56lck, in T cell development was evaluated by mating TCR transgenic mice with transgenic mice that expressed lckF505, a constitutively activated form of p56lck which is under the control of ..
Matrix metalloproteinase-2 and -9 are induced differently by metal nanoparticles in human monocytes: The role of oxidative stress and protein tyrosine kinase activationRong Wan
Department of Environmental Health and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, 555 South Floyd Street, Louisville, KY 40202, USA
Toxicol Appl Pharmacol 233:276-85. 2008..Our results suggest that Nano-Co causes an imbalance between the expression and activity of MMPs and their inhibitors which is mediated by the AP-1 and tyrosine kinase pathways due to oxidative stress...
Solution structure and backbone dynamics of the non-receptor protein-tyrosine kinase-6 Src homology 2 domainEunmi Hong
Department of Biochemistry and Protein Network Research Center, College of Science, Yonsei University, Seoul 120 749, Korea
J Biol Chem 279:29700-8. 2004..The solution structure together with data from the ligand binding mode of PTK6-SH2 provides insight into the molecular basis of the autoinhibitory role of PTK6...
Organization of the human PTK7 gene encoding a receptor protein tyrosine kinase-like molecule and alternative splicing of its mRNAJae Won Jung
National Research Laboratory of Cellular Biochemistry, Department of Biochemistry, College of Science, and Protein Network Research Center, Yonsei University, Seoul, South Korea
Biochim Biophys Acta 1579:153-63. 2002..Our findings suggest that PTK7 is evolutionarily distinct from other RPTKs, and that the alternative splicing of PTK7 mRNA may contribute to its diverse function in cell signaling...
Silica-induced nuclear factor-kappaB activation: involvement of reactive oxygen species and protein tyrosine kinase activationJ L Kang
Department of Physiology, College of Medicine, Ewha Medical Research Center, Ewha Womans University, Seoul, Korea
J Toxicol Environ Health A 60:27-46. 2000..The results suggest that ROS may play a role in silica-induced NF-kappaB activation in macrophages and that phosphorylation events mediated by tyrosine kinase may be involved in this activation...
Mechanism of desensitization of the epidermal growth factor receptor protein-tyrosine kinaseJ L Countaway
Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester 01605
J Biol Chem 267:1129-40. 1992..This regulatory phosphorylation site is located at the carboxyl terminus of the EGF receptor within the subdomain that binds src homology 2 regions of signaling molecules...
Generation of an active protein-tyrosine kinase from lymphocytes by proteolysisT F Zioncheck
Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907
J Biol Chem 263:19195-202. 1988..p72 is also found in certain T and B cell-derived cell lines and in NIH3T3 cells...
Regulation of the human c-fes protein tyrosine kinase (p93c-fes) by its src homology 2 domain and major autophosphorylation site (Tyr-713)S J Hjermstad
Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha 68198 6805
Oncogene 8:2283-92. 1993..These results indicate that the c-fes SH2 domain and consensus autophosphorylation site (Tyr-713) play major roles in the positive regulation of p93c-fes tyrosine kinase activity, possibly through intramolecular interaction...
Frequent activation of the lck gene by promoter insertion and aberrant splicing in murine leukemia virus-induced rat lymphomasS Shin
Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030
Oncogene 8:141-9. 1993..in Fischer rats by Moloney murine leukemia virus for alterations affecting the structure or expression of the lck gene. At least five primary tumors (14%) have a proviral insertion upstream of lck...
Structural analysis of the lymphocyte-specific kinase Lck in complex with non-selective and Src family selective kinase inhibitorsX Zhu
Kinetix Pharmaceuticals, Inc, Medford, MA 02155, USA
Structure 7:651-61. 1999The lymphocyte-specific kinase Lck is a member of the Src family of non-receptor tyrosine kinases. Lck catalyzes the initial phosphorylation of T-cell receptor components that is necessary for signal transduction and T-cell activation...
Retinal dysplasia in mice lacking p56lckB Omri
CNRS UPR 9035, Paris, France
Oncogene 16:2351-6. 1998The product of the proto-oncogene p56lck is a non-receptor tyrosine kinase member of the Src family. It is found in T cells (Marth et al., 1985, 1988) and in the mouse brain (Omri et al., 1996; Van Tan et al., 1996)...
The diabetic BB rat. Neither Th1 nor Th2?D Bellgrau
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, USA
Horm Metab Res 28:299-301. 1996..Our data also indicate that transcript expression for p56lck, an enzyme required for T cell development, is abnormal in BB peripheral T cells...
Hypophosphorylated TCR/CD3zeta signals through a Grb2-SOS1-Ras pathway in Lck knockdown cellsTrond Methi
The Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway
Eur J Immunol 37:2539-48. 2007..signaling events, downstream T cell responses are paradoxically augmented in T cells with siRNA-mediated Lck knockdown (Methi et al., J. Immunol. 2005. 175: 7398-7406)...
Inhibition of p56(lck) tyrosine kinase by isothiazolonesJ M Trevillyan
Abbott Laboratories, Immunological Disease Research, Abbott Park, Illinois, 60064 6119, USA
Arch Biochem Biophys 364:19-29. 1999b>Lck encodes a 56-kDa protein-tyrosine kinase, predominantly expressed in T lymphocytes, crucial for initiating T cell antigen receptor (TCR) signal transduction pathways, culminating in T cell cytokine gene expression and effector ..
Effect of dietary K intake on apical small-conductance K channel in CCD: role of protein tyrosine kinaseY Wei
Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA
Am J Physiol Renal Physiol 281:F206-12. 2001..We conclude that dietary K intake plays a key role in regulating the activity of the SK channels and that PTK is involved in mediating the effect of the K intake on channel activity in the CCD...
The protein-tyrosine kinase Lck associates with and is phosphorylated by Cdc2N I Pathan
Department of Biology, Purdue University, West Lafayette, Indiana 47907, USA
J Biol Chem 271:27517-23. 1996The protein-tyrosine kinase Lck is essential for signaling through the T-cell antigen receptor. Treatment of T-cells with a variety of extracellular stimuli increases the phosphorylation of Lck on serine residues...
Analysis of CD28 cytoplasmic tail tyrosine residues as regulators and substrates for the protein tyrosine kinases, EMT and LCKP D King
The Immunology Program, Sloan Kettering Institute for Cancer Research, New York 10021, USA
J Immunol 158:580-90. 1997..and activation of phosphatidylinositol 3-kinase (PI3-kinase) and activation of the protein tyrosine kinases (PTKs), LCK and EMT...
Expression of p56lck in B-cell neoplasiasA von Knethen
Klinik IV für Nephrologie, Universitat Erlangen, Germany
Leuk Lymphoma 26:551-62. 1997The protooncogene p56lck is considered to participate in malignant transformation of lymphoid cells...
Src tyrosine kinase augments taxotere-induced apoptosis through enhanced expression and phosphorylation of Bcl-2V Boudny
Department of Medicine and Biosystemic Science, Graduate School of Medicine, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka, Fukuoka 812 8582, Japan
Br J Cancer 86:463-9. 2002....
Characterization of the interactions between the active site of a protein tyrosine kinase and a divalent metal activatorXiaofeng Lin
Department of Cell and Molecular Biology, University of Rhode Island, Kingston, RI 02881, USA
BMC Biochem 6:25. 2005..Protein tyrosine kinase Csk requires two Mg2+ cations for activity: one (M1) binds to ATP, and the other (M2) acts as an essential activator...
Role of lymphocyte-specific protein tyrosine kinase (LCK) in the expansion of glioma-initiating cells by fractionated radiationRae Kwon Kim
Department of Chemistry, Research Institute for Natural Sciences, Hanyang University, Seoul, South Korea
Biochem Biophys Res Commun 402:631-6. 2010..In this study, we show that LCK (lymphocyte-specific protein tyrosine kinase) is involved in the fractionated radiation-induced expansion of the ..
The c-Fes protein-tyrosine kinase suppresses cytokine-independent outgrowth of myeloid leukemia cells induced by Bcr-AblJ M Lionberger
Eppley Institute for Research in Cancer and Department of Pathology and Microbiology University of Nebraska Medical Center, Omaha 68198, USA
Cancer Res 60:1097-103. 2000..These results show that Fes and Bcr-Abl interact in myeloid cells, leading to Fes activation and suppression of Bcr-Abl-induced conversion to cytokine independence...
The role of p56lck in the development of gamma delta T cells and their function during an infection by Listeria monocytogenesS Fujise
Department of Immunology, Medical Institute of Bioregulation, Kyusyu University, Fukuoka, Japan
J Immunol 157:247-54. 1996We investigated roles of p56lck tyrosine kinase (Lck) on the development and function of gamma delta T cells in adult mice using lck gene knockout (lck -/-) mice...
Research Grants
- Genetic and Immunological Impact of the HRES-1/Rab4 Locus in SLEAndras Perl; Fiscal Year: 2010..The key intracellular transducer of T-cell activation, Lck, is brought to the IS via binding to CD4. TCR6 chain binds to the TFR...
- p56lck Inhibitors as Potential Immunosuppressive Drugs.ALEXANDER MACKERELL; Fiscal Year: 2004SH2 domains in non-receptor tyrosine kinases, such as p56lck, represent molecular targets that are central to cellular signaling pathways related to immune response...
- TYROSINE PROTEIN KINASES AND LYMPHOCYTE ACTIVATIONROBERT GEAHLEN; Fiscal Year: 1993..It is likely that the molecular mechanisms of signal transduction in B lymphocytes will serve as a prototype for receptor signaling pathways in a variety of cell types...
- TYROSINE PROTEIN KINASES AND LYMPHOCYTE ACTIVATIONROBERT GEAHLEN; Fiscal Year: 1991..It is our contention that a greater understanding of the biochemical pathways that regulate normal cell growth and development is necessary to begin to define the lesions within this pathway that can lead to malignant growth...
- Role of Src Kinases in T Cell Receptor SignalingDavid 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 ..
- Negative regulation of TCR-associated PTKsTomas Mustelin; Fiscal Year: 2006..We will determine to what extent TCR signaling is altered in the absence of PEP and if Lck and Fyn are hyperactive...
- Negative regulation of TCR-associated PTKsROBERT 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...
- Src Family Kinases as Molecular Targets for HIV/NefTHOMAS SMITHGALL; Fiscal Year: 2007..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. ..
- Src Family Kinases as Molecular Targets for HIV/NefTHOMAS 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. ..
- Phosphoproteomic Analysis of T Cell Activation PathwaysARTHUR ROBERT SALOMON; Fiscal Year: 2010..within the pathway through quantitative phosphoproteomic analysis of T cells with disrupted pathway proteins LCK, PLC1, VAV, and ERK...
- OSTEOCLASTIC PHOSPHOTYROSYL PHOSPHATASE AND RESORPTIONKIN HING LAU; Fiscal Year: 2002....
- Focal Adhesion Kinase - Tumor Biology and TherapeuticsWilliam G Cance; Fiscal Year: 2010..Thus, this application will provide novel molecular cancer therapeutics that target the focal adhesion kinase. ..
- INTERFERON SIGNAL TRANSDUCTION IN T CELLSAndrew 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...
- SIGNAL TRANSDUCTION IN T LYMPHOCYTE ACTIVATIONAmnon Altman; Fiscal Year: 1993..the following approaches will be undertaken to elucidate the roles of two T cell-expressed TPKs, p59fyn and p56lck, that are associated with the TCR/CD3 complex or the CD4/CD8 coreceptors, respectively, in T cell signaling, in ..
- PROTEIN TYROSINE KINASE TYRO-3ANNE 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. ..
- REGULATION OF BCR MEDIATED SIGNAL TRANSDUCTION BY CD45LOUIS 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. ..
- T cell regulation by N-glycosylationMichael Demetriou; Fiscal Year: 2010..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)...
- T cell regulation by N-glycosylationMichael Demetriou; Fiscal Year: 2010..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)...
- Mechanisms of Breast Tumor Cell Growth, Motility, and Antiestrogen ResponseAmy Bouton; Fiscal Year: 2009....
- Mechanisms of Breast Tumor Cell Growth, Motility, and Antiestrogen ResponseAmy H Bouton; Fiscal Year: 2010....
- A Tumor Suppressor Function for the c-Fes Tyrosine Kinase in Colon CancerTHOMAS EDWARD SMITHGALL; Fiscal Year: 2010..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. ..
- MITOGENIC SIGNALING BY ENDOTHELIN PEPTIDESMichael Simonson; Fiscal Year: 1993..Because ET-1 has been implicated the vascular response to injury and in renal failure, the ability to block the mitogenic actions of ET might be relevant in clinical settings...
