The scaffolding adapter Gab2, via Shp-2, regulates Kit-evoked mast cell proliferation by activating the Rac/JNK pathway

doi:10.1074/jbc.M603742200

CORC > 北京大学 > 生命科学学院

	The scaffolding adapter Gab2, via Shp-2, regulates Kit-evoked mast cell proliferation by activating the Rac/JNK pathway
	Yu, Min ; Luo, Jincai ; Yang, Wentian ; Wang, Yongping ; Mizuki, Masao ; Kanakura, Yuzuru ; Besmer, Peter ; Neel, Benjamin G. ; Gu, Haihua
刊名	journal of biological chemistry
	2006
DOI	10.1074/jbc.M603742200
英文摘要	The scaffolding adapter Gab2 mediates cell signaling and responses evoked by various extracellular stimuli including several growth factors. Kit, the receptor for stem cell factor (SCF), plays a critical role in the proliferation and differentiation of a variety of cell types, including mast cells. Kit, via Tyr567 and Tyr719, activates Src family kinases (SFK) and PI3K respectively, which converge on the activation of a Rac/JNK pathway required for mast cell proliferation. However, how Kit Tyr567 signals to Rac/JNK is not well understood. By analyzing Gab2-/- mast cells, we find that Gab2 is required for SCF-evoked proliferation, activation of Rac/JNK, and Ras. Upon Kit activation in wild-type mast cells, Gab2 becomes tyrosyl-phosphorylated and associates with Kit and Shp-2. Tyr567, an SFK binding site in Kit, and SFK activity were required for Gab2 tyrosyl phosphorylation and association with Shp-2. By re-expressing Gab2 or a Gab2 mutant that cannot bind Shp-2 in Gab2-/- mast cells or acutely by deleting Shp-2 in mast cells, we found that Gab2 requires Shp-2 for SCF-evoked Rac/JNK, Ras activation, and mast cell proliferation. Lastly, by analyzing mast cells from mice with compound Gab2 and Kit Y719F mutations (i.e.,Gab2 -/-: KitY719F/Y719F mice), we find that Gab2, acting in a parallel pathway to PI3K from Kit Tyr719, regulates mast cell proliferation and development in specific tissues. Our data show that Gab2 via Shp-2 is critical for transmitting signals from Kit Tyr567 to activate the Rac/JNK pathway controlling mast cell proliferation, which likely contributes to mast cell development in specific tissues. ? 2006 by The American Society for Biochemistry and Molecular Biology, Inc.; EI; 0; 39; 28615-28626; 281
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/410116]
专题	生命科学学院
推荐引用方式 GB/T 7714	Yu, Min,Luo, Jincai,Yang, Wentian,et al. The scaffolding adapter Gab2, via Shp-2, regulates Kit-evoked mast cell proliferation by activating the Rac/JNK pathway[J]. journal of biological chemistry,2006.
APA	Yu, Min.,Luo, Jincai.,Yang, Wentian.,Wang, Yongping.,Mizuki, Masao.,...&Gu, Haihua.(2006).The scaffolding adapter Gab2, via Shp-2, regulates Kit-evoked mast cell proliferation by activating the Rac/JNK pathway.journal of biological chemistry.
MLA	Yu, Min,et al."The scaffolding adapter Gab2, via Shp-2, regulates Kit-evoked mast cell proliferation by activating the Rac/JNK pathway".journal of biological chemistry (2006).