Src
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 2.7.10.2; Kinase, protein; Oncoprotein; Protein kinase, TK; Protein kinase, tyrosine (non-receptor); Src family; SrcA subfamily; TK group
Cellular Component: actin filament; anchoring junction; caveola; cell junction; cytoplasm; cytoskeleton; cytosol; dendritic filopodium; dendritic growth cone; extrinsic component of cytoplasmic side of plasma membrane; focal adhesion; glutamatergic synapse; late endosome; lysosome; membrane; mitochondrial inner membrane; mitochondrion; neuronal cell body; nucleoplasm; nucleus; perinuclear region of cytoplasm; plasma membrane; podosome; postsynaptic specialization, intracellular component; ruffle membrane; synaptic membrane
Molecular Function: ATP binding; BMP receptor binding; cell adhesion molecule binding; connexin binding; enzyme binding; ephrin receptor binding; heme binding; insulin receptor binding; integrin binding; kinase activity; non-membrane spanning protein tyrosine kinase activity; nuclear estrogen receptor binding; nucleotide binding; phospholipase activator activity; phospholipase binding; phosphoprotein binding; protein binding; protein domain specific binding; protein kinase activity; protein kinase binding; protein kinase C binding; protein tyrosine kinase activity; protein-containing complex binding; scaffold protein binding; SH2 domain binding; signaling receptor binding; transferase activity; transmembrane transporter binding
Biological Process: activation of protein kinase B activity; angiotensin-activated signaling pathway involved in heart process; bone resorption; branching involved in mammary gland duct morphogenesis; cell adhesion; cell cycle; cell differentiation; cell migration; cellular response to fluid shear stress; cellular response to hydrogen peroxide; cellular response to peptide hormone stimulus; cellular response to platelet-derived growth factor stimulus; cellular response to progesterone stimulus; cellular response to reactive oxygen species; cellular response to transforming growth factor beta stimulus; DNA biosynthetic process; epidermal growth factor receptor signaling pathway; focal adhesion assembly; forebrain development; immune system process; innate immune response; integrin-mediated signaling pathway; interleukin-6-mediated signaling pathway; intestinal epithelial cell development; intracellular signal transduction; negative regulation of anoikis; negative regulation of apoptotic process; negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; negative regulation of DNA-templated transcription; 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-containing complex assembly; negative regulation of telomerase activity; negative regulation of telomere maintenance via telomerase; neurotrophin TRK receptor signaling pathway; odontogenesis; oogenesis; osteoclast development; peptidyl-serine phosphorylation; peptidyl-tyrosine autophosphorylation; peptidyl-tyrosine phosphorylation; phosphorylation; positive regulation of apoptotic process; positive regulation of bone resorption; positive regulation of canonical Wnt signaling pathway; positive regulation of cell adhesion; positive regulation of cyclin-dependent protein serine/threonine kinase activity; positive regulation of cytokine production; positive regulation of dephosphorylation; positive regulation of DNA biosynthetic process; positive regulation of DNA-templated transcription; positive regulation of epithelial cell migration; positive regulation of ERK1 and ERK2 cascade; positive regulation of gene expression; positive regulation of glucose metabolic process; positive regulation of hippo signaling; positive regulation of insulin receptor signaling pathway; positive regulation of intracellular signal transduction; positive regulation of lamellipodium morphogenesis; positive regulation of male germ cell proliferation; positive regulation of MAP kinase activity; positive regulation of Notch signaling pathway; positive regulation of ovarian follicle development; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of phosphatidylinositol 3-kinase activity; 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 protein transport; positive regulation of Ras protein signal transduction; positive regulation of small GTPase mediated signal transduction; positive regulation of smooth muscle cell migration; positive regulation of vascular associated smooth muscle cell proliferation; primary ovarian follicle growth; progesterone receptor signaling pathway; protein autophosphorylation; protein destabilization; protein phosphorylation; 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; response to interleukin-1; stress fiber assembly; substrate adhesion-dependent cell spreading; transcytosis; transforming growth factor beta receptor signaling pathway; uterus development
