Regulatory Network in Protein Phosphorylation
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Kinase: LCK lymphocyte-specific protein tyrosine kinase

Group: TK      Family: Src      Subfamily: SrcB

Description: lymphocyte-specific protein tyrosine kinase

Gene Symbol: LCK

Synonyms: YT16, p56lck, pp58lck

UniprotKB/SwissProt: LCK_HUMAN (P06239)

Function: Tyrosine kinase that plays an essential role for the selection and maturation of developing T-cell in the thymus and in mature T-cell function. Is constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors and plays a key role in T-cell antigen receptor(TCR)-linked signal transduction pathways. 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, and thereby recruits the associated LCK to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosines-based activation motifs (ITAMs) in the cytoplasmic tails of the TCRgamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. In addition, contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, and upon engagement of the CD2 molecule, LCK undergoes hyperphosphorylation and activation. Also plays a role in the IL2 receptor-linked signaling pathway that controls 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.

Subcellular Localization: Cytoplasm. Cell membrane; Lipid-anchor; Cytoplasmic side. Note=Present in lipid rafts in an unactive form.

Protein Domain:
PDB:1BHF

The substrate proteins of kinase LCK

No.Gene NameUniProtKB IDProtein DescriptionNumber of kinase-specific phosphorylation sitesView
1CBLCBL_HUMANE3 ubiquitin-protein ligase CBL (EC 6.3.2.-) (Signal transductionprotein CBL) (Proto-oncogene c-CBL) (Casitas B-lineage lymphoma proto-oncogene) (RING finger protein 55). 3Show
2CD28CD28_HUMANT-cell-specific surface glycoprotein CD28 precursor (TP44). 1Show
3CD33CD33_HUMANMyeloid cell surface antigen CD33 precursor (Sialic acid-binding Ig-like lectin 3) (Siglec-3) (gp67). 1Show
4CD3ECD3E_HUMANT-cell surface glycoprotein CD3 epsilon chain precursor (T-cellsurface antigen T3/Leu-4 epsilon chain). 2Show
5CD5CD5_HUMANT-cell surface glycoprotein CD5 precursor (Lymphocyte antigen T1/Leu-1) (CD5 antigen). 4Show
6CD79BCD79B_HUMANB-cell antigen receptor complex-associated protein beta-chainprecursor (B-cell-specific glycoprotein B29) (Immunoglobulin-associated B29 protein) (IG-beta) (CD79b antigen). 2Show
7CTLA4CTLA4_HUMANCytotoxic T-lymphocyte protein 4 precursor (Cytotoxic T-lymphocyte-associated antigen 4) (CTLA-4) (CD152 antigen). 1Show
8DAPP1DAPP1_HUMANDual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositide (hDAPP1) (B-cell adapter molecule of 32 kDa) (Blymphocyte adapter protein Bam32). 2Show
9DOK1DOK1_HUMANDocking protein 1 (Downstream of tyrosine kinase 1) (p62(dok)) (pp62). 1Show
10ESR1ESR1_HUMANEstrogen receptor (ER) (Estradiol receptor) (ER-alpha) (Nuclearreceptor subfamily 3 group A member 1). 2Show
11VIL2EZRI_HUMANEzrin (p81) (Cytovillin) (Villin-2). 2Show
12NFKBIAIKBA_HUMANNF-kappa-B inhibitor alpha (Major histocompatibility complex enhancer-binding protein MAD3) (I-kappa-B-alpha) (IkappaBalpha) (IkB-alpha). 2Show
13IL2RBIL2RB_HUMANInterleukin-2 receptor subunit beta precursor (IL-2 receptor) (P70-75)(p75) (High affinity IL-2 receptor subunit beta) (CD122 antigen). 10Show
14ITKITK_HUMANTyrosine-protein kinase ITK/TSK (EC 2.7.10.2) (T-cell-specific kinase)(Tyrosine-protein kinase Lyk) (Kinase EMT). 2Show
15PRKCDKPCD_HUMANProtein kinase C delta type (EC 2.7.11.13) (nPKC-delta). 3Show
16PRKCQKPCT_HUMANProtein kinase C theta type (EC 2.7.11.13) (nPKC-theta). 2Show
17LCKLCK_HUMANProto-oncogene tyrosine-protein kinase LCK (EC 2.7.10.2) (p56-LCK)(Lymphocyte cell-specific protein-tyrosine kinase) (LSK) (T cell-specific protein-tyrosine kinase). 3Show
18LCP2LCP2_HUMANLymphocyte cytosolic protein 2 (SH2 domain-containing leukocyteprotein of 76 kDa) (SLP-76 tyrosine phosphoprotein) (SLP76). 2Show
19LIME1LIME1_HUMANLck-interacting transmembrane adapter 1 (Lck-interacting membraneprotein) (Lck-interacting molecule). 1Show
20MRLC2MLRM_HUMANMyosin regulatory light chain 2, nonsarcomeric (Myosin RLC). 1Show
21MYL9MLRN_HUMANMyosin regulatory light chain 2, smooth muscle isoform (Myosin RLC)(Myosin regulatory light chain 9) (LC20). 2Show
22PIK3R1P85A_HUMANPhosphatidylinositol 3-kinase regulatory subunit alpha (PI3-kinase p85subunit alpha) (PtdIns-3-kinase p85-alpha) (PI3K). 1Show
23PLCG2PLCG2_HUMAN1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-2(EC 3.1.4.11) (Phosphoinositide phospholipase C) (PLC-gamma-2)(Phospholipase C-gamma-2) (PLC-IV). 5Show
24ACP1PPAC_HUMANLow molecular weight phosphotyrosine protein phosphatase (EC 3.1.3.48)(LMW-PTPase) (LMW-PTP) (Low molecular weight cytosolic acidphosphatase) (EC 3.1.3.2) (Red cell acid phosphatase 1) (Adipocyteacid phosphatase). 2Show
25PTENPTEN_HUMANPhosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (EC 3.1.3.67) (EC 3.1.3.16)(EC 3.1.3.48) (Phosphatase and tensin homolog) (Mutated in multipleadvanced cancers 1). 2Show
26PTPN6PTN6_HUMANTyrosine-protein phosphatase non-receptor type 6 (EC 3.1.3.48)(Protein-tyrosine phosphatase 1C) (PTP-1C) (Hematopoietic cellprotein-tyrosine phosphatase) (SH-PTP1) (Protein-tyrosine phosphataseSHP-1). 5Show
27RASA1RASA1_HUMANRas GTPase-activating protein 1 (GTPase-activating protein) (GAP) (Rasp21 protein activator) (p120GAP) (RasGAP). 1Show
28SH2B3SH2B3_HUMANSH2B adapter protein 3 (Lymphocyte-specific adapter protein Lnk)(Signal transduction protein Lnk) (Lymphocyte adapter protein). 2Show
29SHC1SHC1_HUMANSHC-transforming protein 1 (SH2 domain protein C1) (Src homology 2domain-containing-transforming protein C1). 2Show
30SIGLEC10SIG10_HUMANSialic acid-binding Ig-like lectin 10 precursor (Siglec-10) (Siglec-like protein 2). 3Show
31SLAMF1SLAF1_HUMANSignaling lymphocytic activation molecule precursor (IPO-3) (CD150antigen) (CDw150). 1Show
32SOCS3SOCS3_HUMANSuppressor of cytokine signaling 3 (SOCS-3) (Cytokine-inducible SH2protein 3) (CIS-3) (STAT-induced STAT inhibitor 3) (SSI-3). 2Show
33SPTAN1SPTA2_HUMANSpectrin alpha chain, brain (Spectrin, non-erythroid alpha chain)(Alpha-II spectrin) (Fodrin alpha chain). 1Show
34STAT1STAT1_HUMANSignal transducer and activator of transcription 1-alpha/beta(Transcription factor ISGF-3 components p91/p84). 2Show
35VAV2VAV2_HUMANProtein vav-2. 3Show
36VAV1VAV_HUMANProto-oncogene vav. 6Show
37ZAP70ZAP70_HUMANTyrosine-protein kinase ZAP-70 (EC 2.7.10.2) (70 kDa zeta-associatedprotein) (Syk-related tyrosine kinase). 11Show