a proto-oncogenic cytoplasmic tyrosine kinase of the SRC family which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Highly expressed in certain fully differentiated cells such as neurons, platelets and macrophages. Participates in signaling pathways that control a diverse spectrum of biological activities including MAPK pathways regulating of growth and differentiation, gene transcription, RNA processing, immune responses, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of plasma membrane receptors and plays a role in the activation and regulation of other protein tyrosine kinases including PTK2, EGFR, FLT4, and DDR2. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. Plays an important role in the regulation of cytoskeletal organization through phosphorylation proteins including AFAP1, RHOA, cortactin (CTTN) and villin. Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal reorganization is also controlled through the phosphorylation of CTTN. When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1. In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1). SRC phosphorylates RNA-binding proteins including KHDRBS1, a major tyrosine phosphoprotein in transformed and growth factor treated cells. Its binding to RNA is significantly impaired following SRC-mediated phosphorylation, suggesting that it may be involved in regulating pre-mRNA-processing. Phosphorylates STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors. Plays a role in EGF-mediated calcium-activated chloride channel activation. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of GRK2, leading to beta-arrestin phosphorylation and internalization. Plays a critical role in the stimulation of the CDK20/ERK1 mitogen-activated protein kinase cascade by epidermal growth factor. Plays an important role in osteoclastic bone resorption in conjunction with PYK2. Both the formation of a SRC-PYK2 complex and SRC kinase activity are necessary for this function. Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase. Required for podosome formation. Phosphorylation of an activation loop tyrosine activates the enzyme; phosphorylation of a tyrosine in the C-terminus by Csk inhibits the enzyme. Expressed ubiquitously. Platelets, neurons and osteoclasts express 5-fold to 200-fold higher levels than most other tissues. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC 184.108.40.206; Kinase, protein; Oncoprotein; Protein kinase, TK; Protein kinase, tyrosine (non-receptor); Src family; TK group
Molecular Function: ATP binding; connexin binding; enzyme binding; ephrin receptor binding; estrogen receptor binding; growth factor receptor binding; heme binding; insulin receptor binding; integrin binding; ion channel binding; kinase activity; kinase binding; non-membrane spanning protein tyrosine kinase activity; phosphoprotein binding; protein binding; protein C-terminus binding; protein kinase activity; protein kinase C binding; protein tyrosine kinase activity; scaffold protein binding; SH2 domain binding; SH3/SH2 adaptor activity; signaling receptor binding; ubiquitin protein ligase binding
Biological Process: activation of protein kinase B activity; adherens junction organization; angiotensin-activated signaling pathway involved in heart process; axon guidance; bone resorption; branching involved in mammary gland duct morphogenesis; cell cycle; cell proliferation; cell-cell adhesion; cellular response to fatty acid; cellular response to fluid shear stress; cellular response to hydrogen peroxide; cellular response to hypoxia; cellular response to insulin stimulus; cellular response to lipopolysaccharide; cellular response to peptide hormone stimulus; cellular response to platelet-derived growth factor stimulus; cellular response to progesterone stimulus; entry of bacterium into host cell; ephrin receptor signaling pathway; epidermal growth factor receptor signaling pathway; ERBB2 signaling pathway; Fc-gamma receptor signaling pathway involved in phagocytosis; forebrain development; G protein-coupled receptor signaling pathway; integrin-mediated signaling pathway; intracellular signal transduction; leukocyte migration; macroautophagy; negative regulation of anoikis; negative regulation of apoptotic process; negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; negative regulation of extrinsic apoptotic signaling pathway; negative regulation of focal adhesion assembly; negative regulation of intrinsic apoptotic signaling pathway; negative regulation of mitochondrial depolarization; negative regulation of protein homooligomerization; negative regulation of telomerase activity; negative regulation of telomere maintenance via telomerase; negative regulation of transcription, DNA-templated; neurotrophin TRK receptor signaling pathway; odontogenesis; oogenesis; peptidyl-serine phosphorylation; peptidyl-tyrosine phosphorylation; platelet activation; positive regulation of apoptotic process; positive regulation of canonical Wnt signaling pathway; positive regulation of cyclin-dependent protein serine/threonine kinase activity; positive regulation of cytokine secretion; positive regulation of DNA biosynthetic process; positive regulation of epithelial cell migration; positive regulation of ERK1 and ERK2 cascade; positive regulation of glucose metabolic process; positive regulation of insulin receptor signaling pathway; positive regulation of integrin activation; positive regulation of lamellipodium morphogenesis; positive regulation of MAP kinase activity; positive regulation of non-membrane spanning protein tyrosine kinase activity; positive regulation of ovarian follicle development; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of phosphatidylinositol 3-kinase activity; positive regulation of phosphatidylinositol 3-kinase signaling; positive regulation of platelet-derived growth factor receptor-beta signaling pathway; positive regulation of podosome assembly; positive regulation of protein autophosphorylation; positive regulation of protein kinase B signaling; positive regulation of protein localization to nucleus; positive regulation of protein processing; positive regulation of protein serine/threonine kinase activity; positive regulation of small GTPase mediated signal transduction; positive regulation of smooth muscle cell migration; positive regulation of transcription, DNA-templated; primary ovarian follicle growth; progesterone receptor signaling pathway; protein autophosphorylation; protein destabilization; regulation of bone resorption; regulation of caveolin-mediated endocytosis; regulation of cell projection assembly; regulation of cell-cell adhesion; regulation of early endosome to late endosome transport; regulation of epithelial cell migration; regulation of intracellular estrogen receptor signaling pathway; regulation of postsynaptic neurotransmitter receptor activity; regulation of protein binding; regulation of vascular permeability; response to acidic pH; response to electrical stimulus; response to interleukin-1; response to mechanical stimulus; response to mineralocorticoid; response to nutrient levels; response to virus; signal complex assembly; signal transduction; stimulatory C-type lectin receptor signaling pathway; stress fiber assembly; substrate adhesion-dependent cell spreading; T cell costimulation; transcytosis; transforming growth factor beta receptor signaling pathway; uterus development; vascular endothelial growth factor receptor signaling pathway; viral process