RRC ID 12765
著者 Futami M, Zhu QS, Whichard ZL, Xia L, Ke Y, Neel BG, Feng GS, Corey SJ.
タイトル G-CSF receptor activation of the Src kinase Lyn is mediated by Gab2 recruitment of the Shp2 phosphatase.
ジャーナル Blood
Abstract Src activation involves the coordinated regulation of positive and negative tyrosine phosphorylation sites. The mechanism whereby receptor tyrosine kinases, cytokine receptors, and integrins activate Src is not known. Here, we demonstrate that granulocyte colony-stimulating factor (G-CSF) activates Lyn, the predominant Src kinase in myeloid cells, through Gab2-mediated recruitment of Shp2. After G-CSF stimulation, Lyn dynamically associates with Gab2 in a spatiotemporal manner. The dephosphorylation of phospho-Lyn Tyr507 was abrogated in Shp2-deficient cells transfected with the G-CSF receptor but intact in cells expressing phosphatase-defective Shp2. Auto-phosphorylation of Lyn Tyr396 was impaired in cells treated with Gab2 siRNA. The constitutively activated Shp2E76A directed the dephosphorylation of phospho-Lyn Tyr507 in vitro. Tyr507 did not undergo dephosphorylation in G-CSF-stimulated cells expressing a mutant Gab2 unable to bind Shp2. We propose that Gab2 forms a complex with Lyn and after G-CSF stimulation, Gab2 recruits Shp2, which dephosphorylates phospho-Lyn Tyr507, leading to Lyn activation.
巻・号 118(4)
ページ 1077-86
公開日 2011-7-28
DOI 10.1182/blood-2009-12-261636
PII S0006-4971(20)44699-3
PMID 21636860
PMC PMC3148159
MeSH Adaptor Proteins, Signal Transducing / metabolism* Animals Cell Separation Enzyme Activation / physiology* Flow Cytometry Humans Immunoblotting Immunoprecipitation Mice Mice, Knockout Phosphorylation Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism* Receptors, Granulocyte Colony-Stimulating Factor / metabolism* Signal Transduction / physiology* Transfection src-Family Kinases / metabolism*
IF 17.794
引用数 29
WOS 分野 HEMATOLOGY
リソース情報
遺伝子材料 pCMV-VSV-G-RSV-Rev (RDB04393)