Linked Life Data

P06239

Source:http://identifiers.org/uniprot/P06239

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
biopax3:comment
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. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. ENZYME REGULATION: The relative activities of the inhibitory tyrosine-protein kinase CSK and the activating tyrosine-protein phosphatase PTPRC/CD45 determine the level of LCK activity. These interactions allow rapid and efficient activation of LCK in response to TCR stimulation. SUBUNIT: Binds to the cytoplasmic domain of cell surface receptors, such as AXL, CD2, CD4, CD5, CD8, CD44, CD45 and CD122. Also binds to effector molecules, such as PI4K, VAV1, RASA1, FYB and to other protein kinases including CDK1, RAF1, ZAP70 and SYK. Binds to phosphatidylinositol 3'-kinase (PI3K) from T-lymphocytes through its SH3 domain and to the tyrosine phosphorylated form of KHDRBS1/p70 through its SH2 domain. Binds to HIV-1 Nef through its SH3 domain. This interaction inhibits its tyrosine-kinase activity. Interacts with SQSTM1. Interacts with phosphorylated LIME1. Interacts with CBLB and PTPRH. Interacts with RUNX3. Forms a signaling complex with EPHA1, PTK2B AND PI3-KINASE; upon activation by EFNA1 which may regulate T-lymphocyte migration. Associates with ZAP70 and RHOH; these interactions allow LCK- mediated RHOH and CD3 subunit phosphorylation in the presence of functional ZAP70. SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Lipid-anchor; Cytoplasmic side. Note=Present in lipid rafts in an unactive form. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=3; Name=Long; IsoId=P06239-1; Sequence=Displayed; Name=Short; IsoId=P06239-2; Sequence=VSP_005000, VSP_005001; Note=No experimental confirmation available; Name=3; IsoId=P06239-3; Sequence=VSP_016049; Note=No experimental confirmation available; TISSUE SPECIFICITY: Expressed specifically in lymphoid cells. DOMAIN: The SH2 domain mediates interaction with SQSTM1. Interaction is regulated by Ser-59 phosphorylation. PTM: Autophosphorylated on Tyr-394, increasing enzymatic activity. Phosphorylated on Tyr-505 by CSK, decreasing activity. Dephosphorylated by PTPRC/CD45. PTM: Myristoylation is required prior to palmitoylation (By similarity). PTM: Palmitoylation regulates subcellular location (By similarity). MASS SPECTROMETRY: Mass=57869.42; Method=MALDI; Range=2-509; Source=PubMed:11840567; DISEASE: Note=A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB. SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. SIMILARITY: Contains 1 protein kinase domain. SIMILARITY: Contains 1 SH2 domain. SIMILARITY: Contains 1 SH3 domain. SEQUENCE CAUTION: Sequence=CAI22320.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=CAI22321.1; Type=Erroneous initiation; Note=Translation N-terminally extended; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/LCKID14ch1p34.html"; WEB RESOURCE: Name=Wikipedia; Note=Lck entry; URL="http://en.wikipedia.org/wiki/Lck"; GENE SYNONYMS:LCK. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License., SEQUENCE 509 AA; 58001 MW; 44BFF0D43FFB420D CRC64;
biopax3:xref
biopax3:displayName
LCK_HUMAN
biopax3:name
2.7.10.2, LCK, LSK, Leukocyte C-terminal Src kinase, Lymphocyte cell-specific protein-tyrosine kinase, Protein YT16, Proto-oncogene Lck, T cell-specific protein-tyrosine kinase, p56-LCK
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biopax3:sequence
MGCGCSSHPEDDWMENIDVCENCHYPIVPLDGKGTLLIRNGSEVRDPLVTYEGSNPPASPLQDNLVIALHSYEPSHDGDLGFEKGEQLRILEQSGEWWKAQSLTTGQEGFIPFNFVAKANSLEPEPWFFKNLSRKDAERQLLAPGNTHGSFLIRESESTAGSFSLSVRDFDQNQGEVVKHYKIRNLDNGGFYISPRITFPGLHELVRHYTNASDGLCTRLSRPCQTQKPQKPWWEDEWEVPRETLKLVERLGAGQFGEVWMGYYNGHTKVAVKSLKQGSMSPDAFLAEANLMKQLQHQRLVRLYAVVTQEPIYIITEYMENGSLVDFLKTPSGIKLTINKLLDMAAQIAEGMAFIEERNYIHRDLRAANILVSDTLSCKIADFGLARLIEDNEYTAREGAKFPIKWTAPEAINYGTFTIKSDVWSFGILLTEIVTHGRIPYPGMTNPEVIQNLERGYRMVRPDNCPEELYQLMRLCWKERPEDRPTFDYLRSVLEDFFTATEGQYQPQP
biopax3:standardName
Tyrosine-protein kinase Lck