FGR

This gene is a member of the Src family of protein tyrosine kinases (PTKs). The encoded protein contains N-terminal sites for myristylation and palmitylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. The protein localizes to plasma membrane ruffles, and functions as a negative regulator of cell migration and adhesion triggered by the beta-2 integrin signal transduction pathway. Infection with Epstein-Barr virus results in the overexpression of this gene. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

FGR Proto-Oncogene, Src Family Tyrosine Kinase

Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors devoid of kinase activity and contributes to the regulation of immune responses, including neutrophil, monocyte, macrophage and mast cell functions, cytoskeleton remodeling in response to extracellular stimuli, phagocytosis, cell adhesion and migration. Promotes mast cell degranulation, release of inflammatory cytokines and IgE-mediated anaphylaxis. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as MS4A2/FCER1B, FCGR2A and/or FCGR2B. Acts downstream of ITGB1 and ITGB2, and regulates actin cytoskeleton reorganization, cell spreading and adhesion. Depending on the context, activates or inhibits cellular responses. Functions as negative regulator of ITGB2 signaling, phagocytosis and SYK activity in monocytes. Required for normal ITGB1 and ITGB2 signaling, normal cell spreading and adhesion in neutrophils and macrophages. Functions as positive regulator of cell migration and regulates cytoskeleton reorganization via RAC1 activation. Phosphorylates SYK (in vitro) and promotes SYK-dependent activation of AKT1 and MAP kinase signaling. Phosphorylates PLD2 in antigen-stimulated mast cells, leading to PLD2 activation and the production of the signaling molecules lysophosphatidic acid and diacylglycerol. Promotes activation of PIK3R1. Phosphorylates FASLG, and thereby regulates its ubiquitination and subsequent internalization. Phosphorylates ABL1. Promotes phosphorylation of CBL, CTTN, PIK3R1, PTK2/FAK1, PTK2B/PYK2 and VAV2. Phosphorylates HCLS1 that has already been phosphorylated by SYK, but not unphosphorylated HCLS1. Together with CLNK, it acts as a negative regulator of natural killer cell-activating receptors and inhibits interferon-gamma production (By similarity).

Bone mineralization Source: Ensembl
Cell differentiation Source: GO_Central
Defense response to Gram-positive bacterium Source: UniProtKB
Fc-gamma receptor signaling pathway involved in phagocytosis Source: Reactome
Immune response-regulating cell surface receptor signaling pathway Source: UniProtKB
Innate immune response Source: GO_Central
Integrin-mediated signaling pathway Source: UniProtKB
Negative regulation of inflammatory response to antigenic stimulus Source: Reactome
Negative regulation of natural killer cell activation Source: Ensembl
Peptidyl-tyrosine phosphorylation Source: UniProtKB
Positive regulation of cell migration Source: UniProtKB
Positive regulation of cytokine production Source: UniProtKB
Positive regulation of mast cell degranulation Source: UniProtKB
Positive regulation of phosphatidylinositol 3-kinase activity Source: UniProtKB
Positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
Protein autophosphorylation Source: UniProtKB
Protein phosphorylation Source: ProtInc
Regulation of cell shape Source: UniProtKB
Regulation of innate immune response Source: UniProtKB
Regulation of phagocytosis Source: UniProtKB
Regulation of protein kinase activity Source: UniProtKB
Response to virus Source: ProtInc
Skeletal system morphogenesis Source: Ensembl
Transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central

Cytoskeleton; Mitochondrion inner membrane; Mitochondrion intermembrane space; Cytosol; Cell membrane; Cell membrane; Ruffle membrane. Detected in mitochondrial intermembrane space and at inner membranes (By similarity). Colocalizes with actin fibers at membrane ruffles. Detected at plasma membrane lipid rafts.

Mutations that cause aberrant kinase activation can confer oncogene activity and promote aberrant cell proliferation.

Ubiquitinated. Becomes ubiquitinated in response to ITGB2 signaling; this does not lead to degradation.
Phosphorylated. Autophosphorylated on tyrosine residues. Becomes phosphorylated in response to FCGR2A and/or FCGR2B engagement, cell adhesion and signaling by ITGB2. Prior phosphorylation at Tyr-523 by SRC inhibits ulterior autophosphorylation at Tyr-412.