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Beschreibung
Macrophage colony-stimulating factor 1 receptor (UniProt: P09581, also known as EC:2.7.10.1, CSF-1 receptor, CSF-1-R, CSF-1R, M-CSF-R, Proto-oncogene c-Fms, CD115) is encoded by the Csf1r (also known as Csfmr, Fms) gene (Gene ID: 12978) in murine species. CSF1R is a single-pass type I membrane glycoprotein that is synthesized with a signal peptide (aa 1-19), which is subsequently cleaved off to produce the mature form that contains an extracellular domain (aa 20-515), a transmembrane domain (aa 516-536), and a cytoplasmic domain (aa 537-977). It is a protein tyrosine kinase that acts as a cell surface receptor for CSF1 and IL-34. It plays an essential role in regulating cell survival, proliferation, and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. It promotes the release of proinflammatory chemokines in response to IL-34 and CSF1, and thereby plays an important role in innate immunity and in inflammatory processes. CSF1R is phosphorylated at multiple tyrosine residues. It is autophosphorylated in response to CSF1 or IL34 binding. Its phosphorylation at Tyr-559 is shown to be important for normal down-regulation of signaling by ubiquitination, internalization, and degradation. Its phosphorylation at Tyr-559 and Tyr-807 is important for interaction with SRC family members, including FYN, YES1 and SRC, and for subsequent activation of these protein kinases. Phosphorylation at Tyr-697 and Tyr-921 is reported to be important for its interaction with Grb2 and its phosphorylation at Tyr-721 is important for interaction with phosphoinositide-3-Kinase Regulatory Subunit 1(PIK3R1. (Ref.: Takeshita, S., et al. (2007). J. Biol. Chem. 282(26), 18980-18990, Sudo, T., et al. (1995). Oncogene. 11(12), 2469-2476, Van der Geer, P., and Hunter, T. (1993), EMBO J. 12(13), 5161-5172).
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