CSF1R - Macrophage colony-stimulating factor 1 receptor - human protein (Function)
 
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CSF1R »  Macrophage colony-stimulating factor 1 receptor
 
Protein also known as:  Proto-oncogene c-Fms; CD antigen CD115.
Gene name:  CSF1R
Entry whose protein(s) existence is based on evidence at protein level
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1 148 2
GENE REF ISO

Function

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Overview 
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.  
15
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
Cytokine bindingdefinition[GO:0019955]  
2
  • UniProtKB
  • BHF-UCL
Macrophage colony-stimulating factor receptor activitydefinition[GO:0005011]  
2
  • UniProtKB
Protein homodimerization activitydefinition[GO:0042803]  
1
  • BHF-UCL
Protein phosphatase bindingdefinition[GO:0019903] silver  
1
  • Ortholog Compara
GO biological process 
Cell proliferationdefinition[GO:0008283]  
1
  • UniProtKB
Cell-cell junction maintenancedefinition[GO:0045217]  
1
  • UniProtKB
Cellular response to cytokine stimulusdefinition[GO:0071345]  
1
  • Ortholog Curator
Cellular response to macrophage colony-stimulating factor stimulusdefinition[GO:0036006]  
2
  • UniProtKB
Cytokine-mediated signaling pathwaydefinition[GO:0019221]  
1
  • UniProtKB
Hemopoiesisdefinition[GO:0030097]  
1
  • UniProtKB
Inflammatory responsedefinition[GO:0006954]  
1
  • UniProtKB
Innate immune responsedefinition[GO:0045087]  
1
  • UniProtKB KW
Macrophage colony-stimulating factor signaling pathwaydefinition[GO:0038145] silver  
1
  • Ortholog Compara
Macrophage differentiationdefinition[GO:0030225]  
1
  • UniProtKB
Mammary gland duct morphogenesisdefinition[GO:0060603]  
1
  • UniProtKB
Monocyte differentiationdefinition[GO:0030224]  
1
  • UniProtKB
Multicellular organismal developmentdefinition[GO:0007275]  
1
  • PINC
Osteoclast differentiationdefinition[GO:0030316]  
1
  • Ortholog Curator
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
1
  • UniProtKB
Phosphatidylinositol metabolic processdefinition[GO:0046488]  
1
  • Ortholog Curator
Phosphatidylinositol-mediated signalingdefinition[GO:0048015]  
1
  • Ortholog Curator
Positive regulation of cell migrationdefinition[GO:0030335]  
1
  • Ortholog Curator
Positive regulation of cell motilitydefinition[GO:2000147]  
1
  • UniProtKB
Positive regulation of cell proliferationdefinition[GO:0008284]  
2
  • UniProtKB
Positive regulation of chemokine secretiondefinition[GO:0090197]  
1
  • UniProtKB
Positive regulation of ERK1 and ERK2 cascadedefinition[GO:0070374]  
1
  • Ortholog Curator
Positive regulation of protein phosphorylationdefinition[GO:0001934]  
1
  • UniProtKB
Positive regulation of protein serine/threonine kinase activitydefinition[GO:0071902]  
1
  • Ortholog Curator
Positive regulation of protein tyrosine kinase activitydefinition[GO:0061098]  
1
  • UniProtKB
Positive regulation of tyrosine phosphorylation of Stat3 proteindefinition[GO:0042517]  
1
  • Ortholog Curator
Protein autophosphorylationdefinition[GO:0046777]  
1
  • UniProtKB
Regulation of actin cytoskeleton reorganizationdefinition[GO:2000249]  
1
  • Ortholog Curator
Regulation of bone resorptiondefinition[GO:0045124]  
1
  • Ortholog Curator
Regulation of cell shapedefinition[GO:0008360]  
1
  • UniProtKB
Ruffle organizationdefinition[GO:0031529]  
1
  • Ortholog Curator
Signal transductiondefinition[GO:0007165]  
1
  • PINC
Transmembrane receptor protein tyrosine kinase signaling pathwaydefinition[GO:0007169]  
1
  • Ortholog Curator
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.1: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
8
  • UniProtKB
  • PROSITE-ProRule
It is regulated in the following manner
Present in an inactive conformation in the absence of bound ligand. CSF1 or IL34 binding leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by imatinib/STI-571 (Gleevec), dasatinib, sunitinib/SU11248, lestaurtinib/CEP-701, midostaurin/PKC-412, Ki20227, linifanib/ABT-869, Axitinib/AG013736, sorafenib/BAY 43-9006 and GW2580.  
8
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Cytokine-cytokine receptor interaction  hsa04060+1436  
Endocytosis  hsa04144+1436  
Hematopoietic cell lineage  hsa04640+1436  
Osteoclast differentiation  hsa04380+1436  
Pathways in cancer  hsa05200+1436  
 

Keywords

Biological process 
Immunity  definition   [KW-0391]
Inflammatory response  definition   [KW-0395]
Innate immunity  definition   [KW-0399]
Molecular function 
Kinase  definition   [KW-0418]
Receptor  definition   [KW-0675]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: Colony_stimulating_factor_1_receptor
GenomeRNAi: 1436
PRO: PR:P07333
Chemistry
GuidetoPHARMACOLOGY: 1806