Protein: Proto-oncogene tyrosine-protein kinase LCK (EC 2.7.10.2) (Lymphocyte cell-specific protein-tyrosine kinase) (p56-LCK) (Q01621)
Organism: Rattus norvegicus (Rat)
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 tyrosine 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 (By similarity). Interacts with UNC119; this interaction plays a crucial role in activation of LCK (By similarity).
Subcellular location: Cell membrane {ECO:0000250|UniProtKB:P06239}; Lipid-anchor {ECO:0000250|UniProtKB:P06239}; Cytoplasmic side {ECO:0000250|UniProtKB:P06239}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:P06239}. Note=Present in lipid rafts in an inactive form. {ECO:0000250|UniProtKB:P06239}.
Interaction partners:
- T-cell surface glycoprotein CD4
- Receptor-type tyrosine-protein phosphatase C
- Tyrosine-protein kinase
- Tyrosine-protein kinase Fyn
- T-cell surface glycoprotein CD8 alpha chain
- Linker for activation of T-cells family member 1
- T-cell surface glycoprotein CD8 beta chain
- T-cell surface glycoprotein CD3 zeta chain
- Growth factor receptor-bound protein 2
- E3 ubiquitin-protein ligase CBL-B
Sequence:
MGCVCSSNPEDDWMENIDVCENCHYPIVPLDSKSTLPIRTGSEVRDPLVTYEGSLPPASPLQDNLVIALHSYEPSHDGDLGFEKGEQLRILEQSGEWWKAQSLTTGQEGFIPFNFVAKANSLEPEPWFFKNLSRKDAERQLLAPGNTHGSFLIRESESTAGSFSLSVRDFDQNQGEVVKHYKIRNLDNGGFYISPRITFPGLHDLVRHYTNASDGLCTKLSRPCQTQKPQKPWWEDEWEVPRETLKLVERLGAGQFGEVWMGYYNGHTKVAVKSLKQGSMSPDAFLAEANLMKQLQHPRLVRLYAVVTQEPIYIITEYMENGSLVDFLKTPSGIKLNVNKLLDMAAQIAEGMAFIEEQNYIHRDLRAANILVSDTLSCKIADFGLARLIEDNEYTAREGAKFPIKWTAPEAINYGTFTIKSDVWSFGILLTEIVTHGRIPYPGMTNPEVIQNLEKGYRMVRPDNCPEELYHLMMLCWKERPEDRPTFDYLRSVLDDFFTATEGQYQPQP