Gastrin stimulates the formation of a p60Src/p125FAK complex upstream of the phosphatidylinositol 3-kinase signaling pathway

被引:35
作者
Daulhac, L [1 ]
Kowalski-Chauvel, A [1 ]
Pradayrol, L [1 ]
Vaysse, N [1 ]
Seva, C [1 ]
机构
[1] CHU Rangueil, Inst Louis Bugnard, Grp Rech Biol & Pathol Digest, INSERM,U151, F-31403 Toulouse, France
关键词
gastrin; G protein-coupled receptor; phosphatidylinositol; 3-kinase; Src-family kinases; focal adhesion kinase; cellular proliferation;
D O I
10.1016/S0014-5793(99)00129-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The molecular events whereby gastrin occupancy of G/CCKB receptors leads to phosphatidylinositol (PI) 3-kinase activation have been examined, We report here that this peptide promotes the association between two non-receptor tyrosine kinases, p60(Src) and p125(FAK), and elicits a parallel increase in tyrosine phosphorylation and activity of both kinases. Gastrin-induced PI 3-kinase activity was coprecipitated with p60(Src) and p125(FAK) and was inhibited by herbimycin A, the selective Src inhibitor PP-2 or cytochalasin D, which disrupts the actin cytoskeleton and prevents p125(FAK) activity. These results indicate, for the first time, that a p60(Src)/p125(FAK) complex acts upstream of the gastrin-stimulated PI 3-kinase pathway, (C) 1999 Federation of European Biochemical Societies.
引用
收藏
页码:251 / 255
页数:5
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