Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines in response to IL34 and CSF1, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone and tooth development. Required for normal male and female fertility, and for normal development of milk ducts and acinar structures in the mammary gland during pregnancy. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration, and promotes cancer cell invasion. Activates several signaling pathways in response to ligand binding. Phosphorylates PIK3R1, PLCG2, GRB2, SLA2 and CBL. Activation of PLCG2 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, that then lead to the activation of protein kinase C family members, especially PRKCD. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to activation of the AKT1 signaling pathway. Activated CSF1R also mediates activation of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1, and of the SRC family kinases SRC, FYN and YES1. Activated CSF1R transmits signals both via proteins that directly interact with phosphorylated tyrosine residues in its intracellular domain, or via adapter proteins, such as GRB2. Promotes activation of STAT family members STAT3, STAT5A and/or STAT5B. Promotes tyrosine phosphorylation of SHC1 and INPP5D/SHIP-1. Receptor signaling is down-regulated by protein phosphatases, such as INPP5D/SHIP-1, that dephosphorylate the receptor and its downstream effectors, and by rapid internalization of the activated receptor. Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily. Expressed in bone marrow and in differentiated blood mononuclear cells. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC 18.104.22.168; Kinase, protein; Membrane protein, integral; Oncoprotein; PDGFR family; Protein kinase, TK; Protein kinase, tyrosine (receptor); TK group
Molecular Function: ATP binding; cytokine binding; macrophage colony-stimulating factor receptor activity; protein binding; protein homodimerization activity; protein phosphatase binding; protein tyrosine kinase activity
Biological Process: axon guidance; cell proliferation; cell-cell junction maintenance; cellular response to cytokine stimulus; cellular response to macrophage colony-stimulating factor stimulus; cytokine-mediated signaling pathway; forebrain neuron differentiation; hemopoiesis; inflammatory response; innate immune response; macrophage colony-stimulating factor signaling pathway; macrophage differentiation; mammary gland duct morphogenesis; microglial cell proliferation; monocyte differentiation; multicellular organism development; negative regulation of apoptotic process; negative regulation of cell proliferation; olfactory bulb development; osteoclast differentiation; peptidyl-tyrosine phosphorylation; phosphatidylinositol metabolic process; phosphatidylinositol-mediated signaling; positive regulation of cell migration; positive regulation of cell motility; positive regulation of cell proliferation; positive regulation of chemokine secretion; positive regulation of ERK1 and ERK2 cascade; positive regulation of protein phosphorylation; positive regulation of protein serine/threonine kinase activity; positive regulation of protein tyrosine kinase activity; positive regulation of tyrosine phosphorylation of STAT protein; protein autophosphorylation; regulation of actin cytoskeleton reorganization; regulation of bone resorption; regulation of cell shape; response to ischemia; ruffle organization; signal transduction; transmembrane receptor protein tyrosine kinase signaling pathway