Lck

Summary

Gene Symbol: Lck
Description: LCK proto-oncogene, Src family tyrosine kinase
Alias: IMD22, LSK, YT16, p56lck, pp58lck, tyrosine-protein kinase Lck, 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
Species: human
Products:     Lck

Top Publications

  1. Lenassi M, Cagney G, Liao M, Vaupotic T, Bartholomeeusen K, Cheng Y, et al. HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4+ T cells. Traffic. 2010;11:110-22 pubmed publisher
    ..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. Heyeck S, Wilcox H, Bunnell S, Berg L. Lck phosphorylates the activation loop tyrosine of the Itk kinase domain and activates Itk kinase activity. J Biol Chem. 1997;272:25401-8 pubmed
    ..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 ..
  3. Criado G, Madrenas J. Superantigen stimulation reveals the contribution of Lck to negative regulation of T cell activation. J Immunol. 2004;172:222-30 pubmed
    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...
  4. Thome M, Duplay P, Guttinger M, Acuto O. Syk and ZAP-70 mediate recruitment of p56lck/CD4 to the activated T cell receptor/CD3/zeta complex. J Exp Med. 1995;181:1997-2006 pubmed
    ..suggested that the association of CD4 with TCR/CD3/zeta requires the interaction of the protein tyrosine kinase p56lck with CD4...
  5. Fackler O, Wolf D, Weber H, Laffert B, D Aloja P, Schuler Thurner B, et al. A natural variability in the proline-rich motif of Nef modulates HIV-1 replication in primary T cells. Curr Biol. 2001;11:1294-9 pubmed
    ..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. ..
  6. Pelosi M, Di Bartolo V, Mounier V, Mege D, Pascussi J, Dufour E, et al. Tyrosine 319 in the interdomain B of ZAP-70 is a binding site for the Src homology 2 domain of Lck. J Biol Chem. 1999;274:14229-37 pubmed
    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...
  7. Housden H, Skipp P, Crump M, Broadbridge R, Crabbe T, Perry M, et al. Investigation of the kinetics and order of tyrosine phosphorylation in the T-cell receptor zeta chain by the protein tyrosine kinase Lck. Eur J Biochem. 2003;270:2369-76 pubmed
    We report experiments to investigate the role of the physiologically relevant protein tyrosine kinase Lck in the ordered phosphorylation of the T-cell receptor zeta chain...
  8. Greenway A, Azad A, Mills J, McPhee D. Human immunodeficiency virus type 1 Nef binds directly to Lck and mitogen-activated protein kinase, inhibiting kinase activity. J Virol. 1996;70:6701-8 pubmed
    ..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)...
  9. Pan X, Rudolph J, Abraham L, Habermann A, Haller C, Krijnse Locker J, et al. HIV-1 Nef compensates for disorganization of the immunological synapse by inducing trans-Golgi network-associated Lck signaling. Blood. 2012;119:786-97 pubmed publisher
    ..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 ..

More Information

Publications66

  1. Jiang Y, Cheng H. Evidence of LAT as a dual substrate for Lck and Syk in T lymphocytes. Leuk Res. 2007;31:541-5 pubmed
    ..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...
  2. Brdicka T, Pavlistová D, Leo A, Bruyns E, Korinek V, Angelisova P, et al. 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. J Exp Med. 2000;191:1591-604 pubmed
    ..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. ..
  3. Abraham L, Bankhead P, Pan X, Engel U, Fackler O. 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. J Immunol. 2012;189:1898-910 pubmed publisher
    ..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. ..
  4. Inngjerdingen M, Torgersen K, Maghazachi A. Lck is required for stromal cell-derived factor 1 alpha (CXCL12)-induced lymphoid cell chemotaxis. Blood. 2002;99:4318-25 pubmed
    ..Damnacanthal, a specific Lck inhibitor, but not the Syk inhibitor piceatannol, inhibited CXCL12-induced chemotaxis of both lymphocyte subsets...
  5. Gorska M, Stafford S, Cen O, Sur S, Alam R. Unc119, a novel activator of Lck/Fyn, is essential for T cell activation. J Exp Med. 2004;199:369-79 pubmed
    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...
  6. Su S, Gong W, Grimm M, Utsunomiya I, Sargeant R, Oppenheim J, et al. Inhibition of tyrosine kinase activation blocks the down-regulation of CXC chemokine receptor 4 by HIV-1 gp120 in CD4+ T cells. J Immunol. 1999;162:7128-32 pubmed
    ..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...
  7. Palacios E, Weiss A. Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation. Oncogene. 2004;23:7990-8000 pubmed
    The function of the Src-family kinases (SFKs) Lck and Fyn in T cells has been intensively studied over the past 15 years...
  8. Chakraborty G, Rangaswami H, Jain S, Kundu G. Hypoxia regulates cross-talk between Syk and Lck leading to breast cancer progression and angiogenesis. J Biol Chem. 2006;281:11322-31 pubmed
    ..The nonreceptor protein-tyrosine kinases Syk and Lck play crucial roles in the signaling mechanism of various cellular processes...
  9. Haller C, Rauch S, Fackler O. HIV-1 Nef employs two distinct mechanisms to modulate Lck subcellular localization and TCR induced actin remodeling. PLoS ONE. 2007;2:e1212 pubmed
    ..spreading and actin polymerization upon TCR engagement, a pronounced intracellular accumulation of the Src kinase Lck and its reduced IS recruitment...
  10. Methi T, Berge T, Torgersen K, Tasken K. Reduced Cbl phosphorylation and degradation of the zeta-chain of the T-cell receptor/CD3 complex in T cells with low Lck levels. Eur J Immunol. 2008;38:2557-63 pubmed publisher
    T cells with short interfering RNA-mediated Lck-knockdown (kd) display paradoxical hyper-responsiveness upon TCR ligation...
  11. Kumar L, Feske S, Rao A, Geha R. A 10-aa-long sequence in SLP-76 upstream of the Gads binding site is essential for T cell development and function. Proc Natl Acad Sci U S A. 2005;102:19063-8 pubmed
    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...
  12. Marie Cardine A, Kirchgessner H, Schraven B. Molecular alterations of the Fyn-complex occur as late events of human T cell activation. Eur J Immunol. 1999;29:1175-87 pubmed
    ..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...
  13. Bruyns E, Marie Cardine A, Kirchgessner H, Sagolla K, Shevchenko A, Mann M, et al. 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. J Exp Med. 1998;188:561-75 pubmed
    ..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. ..
  14. Gotoh N, Toyoda M, Shibuya M. 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. Mol Cell Biol. 1997;17:1824-31 pubmed
    ..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. ..
  15. Schoenborn J, Tan Y, Zhang C, Shokat K, Weiss A. Feedback circuits monitor and adjust basal Lck-dependent events in T cell receptor signaling. Sci Signal. 2011;4:ra59 pubmed publisher
    The Src family kinase Lck is crucial for the initiation of TCR signaling. The activity of Lck is tightly controlled to prevent erroneous immune activation, yet it enables rapid cellular responses over a range of sensitivities to antigens...
  16. Yamaguchi H, Hendrickson W. Structural basis for activation of human lymphocyte kinase Lck upon tyrosine phosphorylation. Nature. 1996;384:484-9 pubmed
    Regulation through phosphorylation is a characteristic of signalling pathways and the lymphocyte kinase Lck (p56lck) both performs phosphorylation and is affected by it...
  17. De Keersmaecker K, Porcu M, Cox L, Girardi T, Vandepoel R, de Beeck J, et al. NUP214-ABL1-mediated cell proliferation in T-cell acute lymphoblastic leukemia is dependent on the LCK kinase and various interacting proteins. Haematologica. 2014;99:85-93 pubmed publisher
    ..In this work, we identify and validate the SRC family kinase LCK as a protein whose activity is absolutely required for the proliferation and survival of T-cell acute lymphoblastic ..
  18. Tapinos N, Rambukkana A. Insights into regulation of human Schwann cell proliferation by Erk1/2 via a MEK-independent and p56Lck-dependent pathway from leprosy bacilli. Proc Natl Acad Sci U S A. 2005;102:9188-93 pubmed
    ..leprae activated Erk1/2 directly by lymphoid cell kinase (p56Lck), a Src family member, by means of a PKCepsilon-dependent and MEK-independent signaling pathway...
  19. Sundvold Gjerstad V, Granum S, Mustelin T, Andersen T, Berge T, Shapiro M, et al. The C terminus of T cell-specific adapter protein (TSAd) is necessary for TSAd-mediated inhibition of Lck activity. Eur J Immunol. 2005;35:1612-20 pubmed
    ..Here, we show that human TSAd interacts with Lck through the Lck SH2 and SH3 domains and is a substrate for Lck...
  20. Shi M, Cooper J, Yu C. A constitutively active Lck kinase promotes cell proliferation and resistance to apoptosis through signal transducer and activator of transcription 5b activation. Mol Cancer Res. 2006;4:39-45 pubmed
    b>Lck is a Src family protein tyrosine kinase and is expressed predominantly in T cells. Aberrant expression or activation of Lck kinase has been reported in both lymphoid and nonlymphoid malignancies...
  21. Molina T, Kishihara K, Siderovski D, van Ewijk W, Narendran A, Timms E, et al. Profound block in thymocyte development in mice lacking p56lck. Nature. 1992;357:161-4 pubmed
    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...
  22. Kabouridis P. 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. Biochem J. 2003;371:907-15 pubmed
    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...
  23. Vila J, Gimferrer I, Padilla O, Arman M, Places L, Simarro M, et al. Residues Y429 and Y463 of the human CD5 are targeted by protein tyrosine kinases. Eur J Immunol. 2001;31:1191-8 pubmed
    ..This is in agreement with data from direct in vitro kinase assays using purified recombinant Lck and Fyn protein tyrosine kinases...
  24. Foster J, Garcia J. Role of Nef in HIV-1 replication and pathogenesis. Adv Pharmacol. 2007;55:389-409 pubmed
  25. Talab F, Allen J, Thompson V, Lin K, Slupsky J. LCK is an important mediator of B-cell receptor signaling in chronic lymphocytic leukemia cells. Mol Cancer Res. 2013;11:541-54 pubmed publisher
    ..Here, we show that CLL cells express lymphocyte-specific protein tyrosine kinase (LCK) and that inhibition of this Src family tyrosine kinase with the specific inhibitor [4-amino-5-(4-phenoxyphenyl)-7H-..
  26. Goldman F, Jensen W, Johnson G, Heasley L, Cambier J. gp120 ligation of CD4 induces p56lck activation and TCR desensitization independent of TCR tyrosine phosphorylation. J Immunol. 1994;153:2905-17 pubmed
    ..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 ..
  27. Witte V, Laffert B, Gintschel P, Krautkrämer E, Blume K, Fackler O, et al. 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. J Immunol. 2008;181:8425-32 pubmed
    ..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]...
  28. Berge T, Sundvold Gjerstad V, Granum S, Andersen T, Holthe G, Claesson Welsh L, et al. T cell specific adapter protein (TSAd) interacts with Tec kinase ITK to promote CXCL12 induced migration of human and murine T cells. PLoS ONE. 2010;5:e9761 pubmed publisher
    ..We show that TSAd is required for tyrosine phosphorylation of the Lck substrate IL2-inducible T cell kinase (Itk)...
  29. Kim R, Yoon C, Hyun K, Lee H, An S, Park M, et al. Role of lymphocyte-specific protein tyrosine kinase (LCK) in the expansion of glioma-initiating cells by fractionated radiation. Biochem Biophys Res Commun. 2010;402:631-6 pubmed publisher
    ..In this study, we show that LCK (lymphocyte-specific protein tyrosine kinase) is involved in the fractionated radiation-induced expansion of the ..
  30. Raab M, Yamamoto M, Rudd C. The T-cell antigen CD5 acts as a receptor and substrate for the protein-tyrosine kinase p56lck. Mol Cell Biol. 1994;14:2862-70 pubmed
    ..In this study, we demonstrate that CD5 is coupled to the protein-tyrosine kinase p56lck and can act as a substrate for p56lck...
  31. Alonso A, Bottini N, Bruckner S, Rahmouni S, Williams S, Schoenberger S, et al. Lck dephosphorylation at Tyr-394 and inhibition of T cell antigen receptor signaling by Yersinia phosphatase YopH. J Biol Chem. 2004;279:4922-8 pubmed
    ..The primary signal transducer for the T cell antigen receptor, the Lck tyrosine kinase, was specifically precipitated by a substrate-trapping YopH mutant, and Lck was dephosphorylated at ..
  32. Saksela K, Cheng G, Baltimore D. 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. EMBO J. 1995;14:484-91 pubmed
    ..Thus, CD4 down-regulation and promotion of viral growth are two distinct functions of Nef, and the latter is mediated via SH3 binding. ..
  33. Bell G, Fargnoli J, Bolen J, Kish L, Imboden J. The SH3 domain of p56lck binds to proline-rich sequences in the cytoplasmic domain of CD2. J Exp Med. 1996;183:169-78 pubmed
    ..An Src-like protein tyrosine kinase, p56lck, coprecipitates with CD2, and perturbation of CD2 by monoclonal antibodies results in an increase in the activity ..
  34. Marie Cardine A, Bruyns E, Eckerskorn C, Kirchgessner H, Meuer S, Schraven B. Molecular cloning of SKAP55, a novel protein that associates with the protein tyrosine kinase p59fyn in human T-lymphocytes. J Biol Chem. 1997;272:16077-80 pubmed
    ..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 ..
  35. Holdorf A, Green J, Levin S, Denny M, Straus D, Link V, et al. Proline residues in CD28 and the Src homology (SH)3 domain of Lck are required for T cell costimulation. J Exp Med. 1999;190:375-84 pubmed
    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...
  36. Giannini A, Bijlmakers M. Regulation of the Src family kinase Lck by Hsp90 and ubiquitination. Mol Cell Biol. 2004;24:5667-76 pubmed
    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...
  37. Marie Cardine A, Kirchgessner H, Bruyns E, Shevchenko A, Mann M, Autschbach F, et al. SHP2-interacting transmembrane adaptor protein (SIT), a novel disulfide-linked dimer regulating human T cell activation. J Exp Med. 1999;189:1181-94 pubmed
    ..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. ..
  38. Bubeck Wardenburg J, Fu C, Jackman J, Flotow H, Wilkinson S, Williams D, et al. Phosphorylation of SLP-76 by the ZAP-70 protein-tyrosine kinase is required for T-cell receptor function. J Biol Chem. 1996;271:19641-4 pubmed
    ..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. ..
  39. Baur A, Sass G, Laffert B, Willbold D, Cheng Mayer C, Peterlin B. The N-terminus of Nef from HIV-1/SIV associates with a protein complex containing Lck and a serine kinase. Immunity. 1997;6:283-91 pubmed
    ..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 ..
  40. Harr M, Caimi P, McColl K, Zhong F, Patel S, Barr P, et al. Inhibition of Lck enhances glucocorticoid sensitivity and apoptosis in lymphoid cell lines and in chronic lymphocytic leukemia. Cell Death Differ. 2010;17:1381-91 pubmed publisher
    ..We have previously shown that the Src family kinase, Lck (lymphocyte cell-specific tyrosine kinase), which is predominantly expressed in T cells, interacts with IP3 ..
  41. Zamoyska R, Basson A, Filby A, Legname G, Lovatt M, Seddon B. The influence of the src-family kinases, Lck and Fyn, on T cell differentiation, survival and activation. Immunol Rev. 2003;191:107-18 pubmed
    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)...
  42. Choi Y, Kim C, Yun Y. Lad, an adapter protein interacting with the SH2 domain of p56lck, is required for T cell activation. J Immunol. 1999;163:5242-9 pubmed
    T cell-specific Src family tyrosine kinase, p56lck, plays crucial roles in T cell differentiation, activation, and proliferation...
  43. Nika K, Tautz L, Arimura Y, Vang T, Williams S, Mustelin T. A weak Lck tail bite is necessary for Lck function in T cell antigen receptor signaling. J Biol Chem. 2007;282:36000-9 pubmed
    ..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 ..
  44. Chiang G, Sefton B. Specific dephosphorylation of the Lck tyrosine protein kinase at Tyr-394 by the SHP-1 protein-tyrosine phosphatase. J Biol Chem. 2001;276:23173-8 pubmed
    ..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...
  45. Filipp D, Zhang J, Leung B, Shaw A, Levin S, Veillette A, et al. Regulation of Fyn through translocation of activated Lck into lipid rafts. J Exp Med. 2003;197:1221-7 pubmed
    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...
  46. Paster W, Paar C, Eckerstorfer P, Jakober A, Drbal K, Schütz G, et al. Genetically encoded Förster resonance energy transfer sensors for the conformation of the Src family kinase Lck. J Immunol. 2009;182:2160-7 pubmed publisher
    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...
  47. Gorska M, Liang Q, Karim Z, Alam R. Uncoordinated 119 protein controls trafficking of Lck via the Rab11 endosome and is critical for immunological synapse formation. J Immunol. 2009;183:1675-84 pubmed publisher
    ..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...
  48. Zimmermann L, Paster W, Weghuber J, Eckerstorfer P, Stockinger H, Schütz G. Direct observation and quantitative analysis of Lck exchange between plasma membrane and cytosol in living T cells. J Biol Chem. 2010;285:6063-70 pubmed publisher
    ..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...
  49. Nika K, Soldani C, Salek M, Paster W, Gray A, Etzensperger R, et al. Constitutively active Lck kinase in T cells drives antigen receptor signal transduction. Immunity. 2010;32:766-77 pubmed publisher
    ..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 ..
  50. Summy J, Gallick G. Src family kinases in tumor progression and metastasis. Cancer Metastasis Rev. 2003;22:337-58 pubmed
    ..Given the ability of Src and its family members to participate in so many aspects of tumor progression and metastasis, Src family kinases are attractive targets for future anti-cancer therapeutics. ..
  51. Garnett D, Barclay A, Carmo A, Beyers A. 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. Eur J Immunol. 1993;23:2540-4 pubmed
    ..are shown to be associated with multimolecular complexes of phosphoproteins including the protein tyrosine kinases p56lck and p60fyn in both rat and mouse thymocytes...
  52. Granum S, Sundvold Gjerstad V, Dai K, Kolltveit K, Hildebrand K, Huitfeldt H, et al. Structure function analysis of SH2D2A isoforms expressed in T cells reveals a crucial role for the proline rich region encoded by SH2D2A exon 7. BMC Immunol. 2006;7:15 pubmed
    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...
  53. Granum S, Andersen T, Sørlie M, Jørgensen M, Koll L, Berge T, et al. Modulation of Lck function through multisite docking to T cell-specific adapter protein. J Biol Chem. 2008;283:21909-19 pubmed publisher
    T cell-specific adapter protein (TSAd), encoded by the SH2D2A gene, interacts with Lck through its C terminus and thus modulates Lck activity...
  54. Seavitt J, White L, Murphy K, Loh D, Perlmutter R, Thomas M. Expression of the p56(Lck) Y505F mutation in CD45-deficient mice rescues thymocyte development. Mol Cell Biol. 1999;19:4200-8 pubmed
    ..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...
  55. D Oro U, Ashwell J. Cutting edge: the CD45 tyrosine phosphatase is an inhibitor of Lck activity in thymocytes. J Immunol. 1999;162:1879-83 pubmed
    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)...
  56. Liu Y, Witte S, Liu Y, Doyle M, Elly C, Altman A. Regulation of protein kinase Ctheta function during T cell activation by Lck-mediated tyrosine phosphorylation. J Biol Chem. 2000;275:3603-9 pubmed
    ..CD3 activation. The Src family protein-tyrosine kinase, Lck, was critical in TCR-induced tyrosine phosphorylation of PKCtheta...
  57. Mahabeleshwar G, Kundu G. 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. J Biol Chem. 2003;278:52598-612 pubmed
    ..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 ..