| http://purl.uniprot.org/citations/22375015 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22375015 | http://www.w3.org/2000/01/rdf-schema#comment | "Colony-stimulating factor-1 (CSF-1)-stimulated CSF-1 receptor (CSF-1R) tyrosine phosphorylation initiates survival, proliferation, and differentiation signaling pathways in macrophages. Either activation loop Y807F or juxtamembrane domain (JMD) Y559F mutations severely compromise CSF-1-regulated proliferation and differentiation. YEF, a CSF-1R in which all eight tyrosines phosphorylated in the activated receptor were mutated to phenylalanine, lacks in vitro kinase activity and in vivo CSF-1-regulated tyrosine phosphorylation. The addition of Tyr-807 alone to the YEF backbone (Y807AB) led to CSF-1-independent but receptor kinase-dependent proliferation, without detectable activation loop Tyr-807 phosphorylation. The addition of Tyr-559 alone (Y559AB) supported a low level of CSF-1-independent proliferation that was slightly enhanced by CSF-1, indicating that Tyr-559 has a positive Tyr-807-independent effect. Consistent with the postulated autoinhibitory role of the JMD Tyr-559 and its relief by ligand-induced Tyr-559 phosphorylation, the addition of Tyr-559 to the Y807AB background suppressed proliferation in the absence of CSF-1, but restored most of the CSF-1-stimulated proliferation. Full restoration of kinase activation and proliferation required the additional add back of JMD Tyr-544. Inhibitor experiments indicate that the constitutive proliferation of Y807AB macrophages is mediated by the phosphatidylinositol 3-kinase (PI3K) and ERK1/2 pathways, whereas proliferation of WT and Y559,807AB macrophages is, in addition, contributed to by Src family kinase (SFK)-dependent pathways. Thus Tyr-807 confers sufficient kinase activity for strong CSF-1-independent proliferation, whereas Tyr-559 maintains the receptor in an inactive state. Tyr-559 phosphorylation releases this restraint and may also contribute to the CSF-1-regulated proliferative response by activating Src family kinase."xsd:string |
| http://purl.uniprot.org/citations/22375015 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m112.355610"xsd:string |
| http://purl.uniprot.org/citations/22375015 | http://purl.uniprot.org/core/author | "Chen J."xsd:string |
| http://purl.uniprot.org/citations/22375015 | http://purl.uniprot.org/core/author | "Yu W."xsd:string |
| http://purl.uniprot.org/citations/22375015 | http://purl.uniprot.org/core/author | "Xiong Y."xsd:string |
| http://purl.uniprot.org/citations/22375015 | http://purl.uniprot.org/core/author | "Pixley F.J."xsd:string |
| http://purl.uniprot.org/citations/22375015 | http://purl.uniprot.org/core/author | "Stanley E.R."xsd:string |
| http://purl.uniprot.org/citations/22375015 | http://purl.uniprot.org/core/author | "Yeung Y.G."xsd:string |
| http://purl.uniprot.org/citations/22375015 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22375015 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/22375015 | http://purl.uniprot.org/core/pages | "13694-13704"xsd:string |
| http://purl.uniprot.org/citations/22375015 | http://purl.uniprot.org/core/title | "Macrophage proliferation is regulated through CSF-1 receptor tyrosines 544, 559, and 807."xsd:string |
| http://purl.uniprot.org/citations/22375015 | http://purl.uniprot.org/core/volume | "287"xsd:string |
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