Tyrosine-protein kinase Lck

Details

Name
Tyrosine-protein kinase Lck
Synonyms
  • 2.7.10.2
  • Leukocyte C-terminal Src kinase
  • LSK
  • Lymphocyte cell-specific protein-tyrosine kinase
  • p56-LCK
  • Protein YT16
  • Proto-oncogene Lck
  • T cell-specific protein-tyrosine kinase
Gene Name
LCK
Organism
Humans
Amino acid sequence
>lcl|BSEQ0037093|Tyrosine-protein kinase Lck
MGCGCSSHPEDDWMENIDVCENCHYPIVPLDGKGTLLIRNGSEVRDPLVTYEGSNPPASP
LQDNLVIALHSYEPSHDGDLGFEKGEQLRILEQSGEWWKAQSLTTGQEGFIPFNFVAKAN
SLEPEPWFFKNLSRKDAERQLLAPGNTHGSFLIRESESTAGSFSLSVRDFDQNQGEVVKH
YKIRNLDNGGFYISPRITFPGLHELVRHYTNASDGLCTRLSRPCQTQKPQKPWWEDEWEV
PRETLKLVERLGAGQFGEVWMGYYNGHTKVAVKSLKQGSMSPDAFLAEANLMKQLQHQRL
VRLYAVVTQEPIYIITEYMENGSLVDFLKTPSGIKLTINKLLDMAAQIAEGMAFIEERNY
IHRDLRAANILVSDTLSCKIADFGLARLIEDNEYTAREGAKFPIKWTAPEAINYGTFTIK
SDVWSFGILLTEIVTHGRIPYPGMTNPEVIQNLERGYRMVRPDNCPEELYQLMRLCWKER
PEDRPTFDYLRSVLEDFFTATEGQYQPQP
Number of residues
509
Molecular Weight
58000.15
Theoretical pI
5.03
GO Classification
Functions
antigen binding / ATP binding / ATPase binding / CD4 receptor binding / CD8 receptor binding / glycoprotein binding / identical protein binding / non-membrane spanning protein tyrosine kinase activity / phosphatidylinositol 3-kinase binding / protein C-terminus binding / protein kinase binding / protein phosphatase binding / protein serine/threonine phosphatase activity / protein tyrosine kinase activity / SH2 domain binding
Processes
activation of cysteine-type endopeptidase activity involved in apoptotic process / aging / B cell receptor signaling pathway / blood coagulation / cellular response to peptide hormone stimulus / cellular zinc ion homeostasis / epidermal growth factor receptor signaling pathway / Fc-epsilon receptor signaling pathway / fibroblast growth factor receptor signaling pathway / hemopoiesis / innate immune response / leukocyte migration / neurotrophin TRK receptor signaling pathway / peptidyl-tyrosine autophosphorylation / phosphatidylinositol-mediated signaling / platelet activation / positive regulation of gamma-delta T cell differentiation / positive regulation of gene expression / positive regulation of intrinsic apoptotic signaling pathway / positive regulation of T cell activation / positive regulation of T cell receptor signaling pathway / positive regulation of tyrosine phosphorylation of Stat5 protein / positive regulation of uterine smooth muscle contraction / protein dephosphorylation / protein phosphorylation / regulation of cell proliferation / regulation of defense response to virus by virus / regulation of lymphocyte activation / release of sequestered calcium ion into cytosol / response to drug / response to hydrogen peroxide / response to mechanical stimulus / response to zinc ion / T cell costimulation / T cell differentiation / T cell receptor signaling pathway / transmembrane receptor protein tyrosine kinase signaling pathway / viral process
Components
cell-cell junction / cytosol / endocytic vesicle / extracellular exosome / extrinsic component of cytoplasmic side of plasma membrane / immunological synapse / membrane raft / pericentriolar material / plasma membrane
General Function
Sh2 domain binding
Specific Function
Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0020487|Tyrosine-protein kinase Lck (LCK)
ATGGGCTGTGGCTGCAGCTCACACCCGGAAGATGACTGGATGGAAAACATCGATGTGTGT
GAGAACTGCCATTATCCCATAGTCCCACTGGATGGCAAGGGCACGCTGCTCATCCGAAAT
GGCTCTGAGGTGCGGGACCCACTGGTTACCTACGAAGGCTCCAATCCGCCGGCTTCCCCA
CTGCAAGACAACCTGGTTATCGCTCTGCACAGCTATGAGCCCTCTCACGACGGAGATCTG
GGCTTTGAGAAGGGGGAACAGCTCCGCATCCTGGAGCAGAGCGGCGAGTGGTGGAAGGCG
CAGTCCCTGACCACGGGCCAGGAAGGCTTCATCCCCTTCAATTTTGTGGCCAAAGCGAAC
AGCCTGGAGCCCGAACCCTGGTTCTTCAAGAACCTGAGCCGCAAGGACGCGGAGCGGCAG
CTCCTGGCGCCCGGGAACACTCACGGCTCCTTCCTCATCCGGGAGAGCGAGAGCACCGCG
GGATCGTTTTCACTGTCGGTCCGGGACTTCGACCAGAACCAGGGAGAGGTGGTGAAACAT
TACAAGATCCGTAATCTGGACAACGGTGGCTTCTACATCTCCCCTCGAATCACTTTTCCC
GGCCTGCATGAACTGGTCCGCCATTACACCAATGCTTCAGATGGGCTGTGCACACGGTTG
AGCCGCCCCTGCCAGACCCAGAAGCCCCAGAAGCCGTGGTGGGAGGACGAGTGGGAGGTT
CCCAGGGAGACGCTGAAGCTGGTGGAGCGGCTGGGGGCTGGACAGTTCGGGGAGGTGTGG
ATGGGGTACTACAACGGGCACACGAAGGTGGCGGTGAAGAGCCTGAAGCAGGGCAGCATG
TCCCCGGACGCCTTCCTGGCCGAGGCCAACCTCATGAAGCAGCTGCAACACCAGCGGCTG
GTTCGGCTCTACGCTGTGGTCACCCAGGAGCCCATCTACATCATCACTGAATACATGGAG
AATGGGAGTCTAGTGGATTTTCTCAAGACCCCTTCAGGCATCAAGTTGACCATCAACAAA
CTCCTGGACATGGCAGCCCAAATTGCAGAAGGCATGGCATTCATTGAAGAGCGGAATTAT
ATTCATCGTGACCTTCGGGCTGCCAACATTCTGGTGTCTGACACCCTGAGCTGCAAGATT
GCAGACTTTGGCCTAGCACGCCTCATTGAGGACAACGAGTACACAGCCAGGGAGGGGGCC
AAGTTTCCCATTAAGTGGACAGCGCCAGAAGCCATTAACTACGGGACATTCACCATCAAG
TCAGATGTGTGGTCTTTTGGGATCCTGCTGACGGAAATTGTCACCCACGGCCGCATCCCT
TACCCAGGGATGACCAACCCGGAGGTGATTCAGAACCTGGAGCGAGGCTACCGCATGGTG
CGCCCTGACAACTGTCCAGAGGAGCTGTACCAACTCATGAGGCTGTGCTGGAAGGAGCGC
CCAGAGGACCGGCCCACCTTTGACTACCTGCGCAGTGTGCTGGAGGACTTCTTCACGGCC
ACAGAGGGCCAGTACCAGCCTCAGCCTTGA
Chromosome Location
1
Locus
1p34.3
External Identifiers
ResourceLink
UniProtKB IDP06239
UniProtKB Entry NameLCK_HUMAN
GenBank Protein ID36808
GenBank Gene IDX05027
GenAtlas IDLCK
HGNC IDHGNC:6524
General References
  1. Koga Y, Caccia N, Toyonaga B, Spolski R, Yanagi Y, Yoshikai Y, Mak TW: A human T cell-specific cDNA clone (YT16) encodes a protein with extensive homology to a family of protein-tyrosine kinases. Eur J Immunol. 1986 Dec;16(12):1643-6. [Article]
  2. Perlmutter RM, Marth JD, Lewis DB, Peet R, Ziegler SF, Wilson CB: Structure and expression of lck transcripts in human lymphoid cells. J Cell Biochem. 1988 Oct;38(2):117-26. [Article]
  3. Rouer E, Van Huynh T, Lavareda de Souza S, Lang MC, Fischer S, Benarous R: Structure of the human lck gene: differences in genomic organisation within src-related genes affect only N-terminal exons. Gene. 1989 Dec 7;84(1):105-13. [Article]
  4. Wright DD, Sefton BM, Kamps MP: Oncogenic activation of the Lck protein accompanies translocation of the LCK gene in the human HSB2 T-cell leukemia. Mol Cell Biol. 1994 Apr;14(4):2429-37. [Article]
  5. Vogel LB, Arthur R, Fujita DJ: An aberrant lck mRNA in two human T-cell lines. Biochim Biophys Acta. 1995 Nov 7;1264(2):168-72. [Article]
  6. Nervi S, Nicodeme S, Gartioux C, Atlan C, Lathrop M, Reviron D, Naquet P, Matsuda F, Imbert J, Vialettes B: No association between lck gene polymorphisms and protein level in type 1 diabetes. Diabetes. 2002 Nov;51(11):3326-30. [Article]
  7. Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. [Article]
  8. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  9. Garvin AM, Pawar S, Marth JD, Perlmutter RM: Structure of the murine lck gene and its rearrangement in a murine lymphoma cell line. Mol Cell Biol. 1988 Aug;8(8):3058-64. [Article]
  10. Takadera T, Leung S, Gernone A, Koga Y, Takihara Y, Miyamoto NG, Mak TW: Structure of the two promoters of the human lck gene: differential accumulation of two classes of lck transcripts in T cells. Mol Cell Biol. 1989 May;9(5):2173-80. [Article]
  11. Boncristiano M, Majolini MB, D'Elios MM, Pacini S, Valensin S, Ulivieri C, Amedei A, Falini B, Del Prete G, Telford JL, Baldari CT: Defective recruitment and activation of ZAP-70 in common variable immunodeficiency patients with T cell defects. Eur J Immunol. 2000 Sep;30(9):2632-8. [Article]
  12. Veillette A, Foss FM, Sausville EA, Bolen JB, Rosen N: Expression of the lck tyrosine kinase gene in human colon carcinoma and other non-lymphoid human tumor cell lines. Oncogene Res. 1987 Sep-Oct;1(4):357-74. [Article]
  13. Trevillyan JM, Lin Y, Chen SJ, Phillips CA, Canna C, Linna TJ: Human T lymphocytes express a protein-tyrosine kinase homologous to p56LSTRA. Biochim Biophys Acta. 1986 Oct 10;888(3):286-95. [Article]
  14. Bergman M, Mustelin T, Oetken C, Partanen J, Flint NA, Amrein KE, Autero M, Burn P, Alitalo K: The human p50csk tyrosine kinase phosphorylates p56lck at Tyr-505 and down regulates its catalytic activity. EMBO J. 1992 Aug;11(8):2919-24. [Article]
  15. Vogel LB, Fujita DJ: The SH3 domain of p56lck is involved in binding to phosphatidylinositol 3'-kinase from T lymphocytes. Mol Cell Biol. 1993 Dec;13(12):7408-17. [Article]
  16. Vogel LB, Fujita DJ: p70 phosphorylation and binding to p56lck is an early event in interleukin-2-induced onset of cell cycle progression in T-lymphocytes. J Biol Chem. 1995 Feb 10;270(6):2506-11. [Article]
  17. Park I, Chung J, Walsh CT, Yun Y, Strominger JL, Shin J: Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56lck and its regulation by phosphorylation of Ser-59 in the lck unique N-terminal region. Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12338-42. [Article]
  18. Bougeret C, Delaunay T, Romero F, Jullien P, Sabe H, Hanafusa H, Benarous R, Fischer S: 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. J Biol Chem. 1996 Mar 29;271(13):7465-72. [Article]
  19. 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 Oct;70(10):6701-8. [Article]
  20. Braunger J, Schleithoff L, Schulz AS, Kessler H, Lammers R, Ullrich A, Bartram CR, Janssen JW: Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site. Oncogene. 1997 Jun 5;14(22):2619-31. [Article]
  21. Isakov N, Biesinger B: Lck protein tyrosine kinase is a key regulator of T-cell activation and a target for signal intervention by Herpesvirus saimiri and other viral gene products. Eur J Biochem. 2000 Jun;267(12):3413-21. [Article]
  22. Yasuda K, Nagafuku M, Shima T, Okada M, Yagi T, Yamada T, Minaki Y, Kato A, Tani-Ichi S, Hamaoka T, Kosugi A: Cutting edge: Fyn is essential for tyrosine phosphorylation of Csk-binding protein/phosphoprotein associated with glycolipid-enriched microdomains in lipid rafts in resting T cells. J Immunol. 2002 Sep 15;169(6):2813-7. [Article]
  23. Harris RA, Yang A, Stein RC, Lucy K, Brusten L, Herath A, Parekh R, Waterfield MD, O'Hare MJ, Neville MA, Page MJ, Zvelebil MJ: Cluster analysis of an extensive human breast cancer cell line protein expression map database. Proteomics. 2002 Feb;2(2):212-23. [Article]
  24. Brdickova N, Brdicka T, Angelisova P, Horvath O, Spicka J, Hilgert I, Paces J, Simeoni L, Kliche S, Merten C, Schraven B, Horejsi V: LIME: a new membrane Raft-associated adaptor protein involved in CD4 and CD8 coreceptor signaling. J Exp Med. 2003 Nov 17;198(10):1453-62. Epub 2003 Nov 10. [Article]
  25. Hur EM, Son M, Lee OH, Choi YB, Park C, Lee H, Yun Y: LIME, a novel transmembrane adaptor protein, associates with p56lck and mediates T cell activation. J Exp Med. 2003 Nov 17;198(10):1463-73. Epub 2003 Nov 10. [Article]
  26. Ito T, Okazawa H, Maruyama K, Tomizawa K, Motegi S, Ohnishi H, Kuwano H, Kosugi A, Matozaki T: Interaction of SAP-1, a transmembrane-type protein-tyrosine phosphatase, with the tyrosine kinase Lck. Roles in regulation of T cell function. J Biol Chem. 2003 Sep 12;278(37):34854-63. Epub 2003 Jul 1. [Article]
  27. Gorska MM, Stafford SJ, Cen O, Sur S, Alam R: Unc119, a novel activator of Lck/Fyn, is essential for T cell activation. J Exp Med. 2004 Feb 2;199(3):369-79. Epub 2004 Jan 23. [Article]
  28. Gelkop S, Gish GD, Babichev Y, Pawson T, Isakov N: T cell activation-induced CrkII binding to the Zap70 protein tyrosine kinase is mediated by Lck-dependent phosphorylation of Zap70 tyrosine 315. J Immunol. 2005 Dec 15;175(12):8123-32. [Article]
  29. Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ: Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol. 2005 Jan;23(1):94-101. Epub 2004 Dec 12. [Article]
  30. Wu J, Katrekar A, Honigberg LA, Smith AM, Conn MT, Tang J, Jeffery D, Mortara K, Sampang J, Williams SR, Buggy J, Clark JM: Identification of substrates of human protein-tyrosine phosphatase PTPN22. J Biol Chem. 2006 Apr 21;281(16):11002-10. Epub 2006 Feb 6. [Article]
  31. Mason LH, Willette-Brown J, Taylor LS, McVicar DW: Regulation of Ly49D/DAP12 signal transduction by Src-family kinases and CD45. J Immunol. 2006 Jun 1;176(11):6615-23. [Article]
  32. Hjorthaug HS, Aasheim HC: Ephrin-A1 stimulates migration of CD8+CCR7+ T lymphocytes. Eur J Immunol. 2007 Aug;37(8):2326-36. [Article]
  33. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
  34. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [Article]
  35. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
  36. Goh YM, Cinghu S, Hong ET, Lee YS, Kim JH, Jang JW, Li YH, Chi XZ, Lee KS, Wee H, Ito Y, Oh BC, Bae SC: Src kinase phosphorylates RUNX3 at tyrosine residues and localizes the protein in the cytoplasm. J Biol Chem. 2010 Mar 26;285(13):10122-9. doi: 10.1074/jbc.M109.071381. Epub 2010 Jan 25. [Article]
  37. Collins M, Tremblay M, Chapman N, Curtiss M, Rothman PB, Houtman JC: The T cell receptor-mediated phosphorylation of Pyk2 tyrosines 402 and 580 occurs via a distinct mechanism than other receptor systems. J Leukoc Biol. 2010 Apr;87(4):691-701. doi: 10.1189/jlb.0409227. Epub 2009 Dec 22. [Article]
  38. Wang H, Zeng X, Fan Z, Lim B: RhoH modulates pre-TCR and TCR signalling by regulating LCK. Cell Signal. 2011 Jan;23(1):249-58. doi: 10.1016/j.cellsig.2010.09.009. Epub 2010 Sep 16. [Article]
  39. Wiede F, Shields BJ, Chew SH, Kyparissoudis K, van Vliet C, Galic S, Tremblay ML, Russell SM, Godfrey DI, Tiganis T: T cell protein tyrosine phosphatase attenuates T cell signaling to maintain tolerance in mice. J Clin Invest. 2011 Dec;121(12):4758-74. doi: 10.1172/JCI59492. Epub 2011 Nov 14. [Article]
  40. Scales TM, Derkinderen P, Leung KY, Byers HL, Ward MA, Price C, Bird IN, Perera T, Kellie S, Williamson R, Anderton BH, Reynolds CH: Tyrosine phosphorylation of tau by the SRC family kinases lck and fyn. Mol Neurodegener. 2011 Jan 26;6:12. doi: 10.1186/1750-1326-6-12. [Article]
  41. Schoenborn JR, Tan YX, Zhang C, Shokat KM, Weiss A: Feedback circuits monitor and adjust basal Lck-dependent events in T cell receptor signaling. Sci Signal. 2011 Sep 13;4(190):ra59. doi: 10.1126/scisignal.2001893. [Article]
  42. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [Article]
  43. Strunk U, Saffran HA, Wu FW, Smiley JR: Role of herpes simplex virus VP11/12 tyrosine-based motifs in binding and activation of the Src family kinase Lck and recruitment of p85, Grb2, and Shc. J Virol. 2013 Oct;87(20):11276-86. doi: 10.1128/JVI.01702-13. Epub 2013 Aug 14. [Article]
  44. Eck MJ, Atwell SK, Shoelson SE, Harrison SC: Structure of the regulatory domains of the Src-family tyrosine kinase Lck. Nature. 1994 Apr 21;368(6473):764-9. [Article]
  45. Mikol V, Baumann G, Keller TH, Manning U, Zurini MG: The crystal structures of the SH2 domain of p56lck complexed with two phosphonopeptides suggest a gated peptide binding site. J Mol Biol. 1995 Feb 17;246(2):344-55. [Article]
  46. Tong L, Warren TC, King J, Betageri R, Rose J, Jakes S: Crystal structures of the human p56lck SH2 domain in complex with two short phosphotyrosyl peptides at 1.0 A and 1.8 A resolution. J Mol Biol. 1996 Mar 1;256(3):601-10. [Article]
  47. Yamaguchi H, Hendrickson WA: Structural basis for activation of human lymphocyte kinase Lck upon tyrosine phosphorylation. Nature. 1996 Dec 5;384(6608):484-9. [Article]
  48. Tong L, Warren TC, Lukas S, Schembri-King J, Betageri R, Proudfoot JR, Jakes S: Carboxymethyl-phenylalanine as a replacement for phosphotyrosine in SH2 domain binding. J Biol Chem. 1998 Aug 7;273(32):20238-42. [Article]
  49. Hauck F, Randriamampita C, Martin E, Gerart S, Lambert N, Lim A, Soulier J, Maciorowski Z, Touzot F, Moshous D, Quartier P, Heritier S, Blanche S, Rieux-Laucat F, Brousse N, Callebaut I, Veillette A, Hivroz C, Fischer A, Latour S, Picard C: Primary T-cell immunodeficiency with immunodysregulation caused by autosomal recessive LCK deficiency. J Allergy Clin Immunol. 2012 Nov;130(5):1144-1152.e11. doi: 10.1016/j.jaci.2012.07.029. Epub 2012 Sep 15. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01254Dasatinibapproved, investigationalyesinhibitormultitargetDetails
DB01830AP-22408experimentalunknownDetails
DB02010StaurosporineexperimentalunknownDetails
DB030231-Tert-Butyl-3-(4-Chloro-Phenyl)-1h-Pyrazolo[3,4-D]Pyrimidin-4-YlamineexperimentalunknownDetails
DB04003{4-[(2S)-2-Acetamido-3-({(1S)-1-[3-carbamoyl-4-(cyclohexylmethoxy)phenyl]ethyl}amino)-3-oxopropyl]-2-phosphonophenoxy}acetic acidexperimentalunknownDetails
DB04395Phosphoaminophosphonic Acid-Adenylate EsterexperimentalunknownDetails
DB069253-(2-AMINOQUINAZOLIN-6-YL)-4-METHYL-N-[3-(TRIFLUOROMETHYL)PHENYL]BENZAMIDEexperimentalunknownDetails
DB071462,3-DIPHENYL-N-(2-PIPERAZIN-1-YLETHYL)FURO[2,3-B]PYRIDIN-4-AMINEexperimentalunknownDetails
DB072975,6-DIPHENYL-N-(2-PIPERAZIN-1-YLETHYL)FURO[2,3-D]PYRIMIDIN-4-AMINEexperimentalunknownDetails
DB08055N-(2-chlorophenyl)-5-phenylimidazo[1,5-a]pyrazin-8-amineexperimentalunknownDetails
DB08056N-(2,6-dimethylphenyl)-5-phenylimidazo[1,5-a]pyrazin-8-amineexperimentalunknownDetails
DB08057N-(2-chloro-6-methylphenyl)-8-[(3S)-3-methylpiperazin-1-yl]imidazo[1,5-a]quinoxalin-4-amineexperimentalunknownDetails
DB08901Ponatinibapproved, investigationalunknowninhibitorDetails
DB09079NintedanibapprovedunknowninhibitorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB15035Zanubrutinibapproved, investigationalunknowninhibitorDetails
DB16656ZotiraciclibinvestigationalunknowninhibitorDetails