Activated phosphatidylinositol 3-kinase is sufficient to mediate actin rearrangement and GLUT4 translocation in 3T3-L1 adipocytes

被引:187
作者
Martin, SS
Haruta, T
Morris, AJ
Klippel, A
Williams, LT
Olefsky, JM
机构
[1] UNIV CALIF SAN DIEGO,DEPT MED 9111G,VET ADM MED CTR,DIV ENDOCRINOL & METAB,LA JOLLA,CA 92093
[2] CHIRON CORP,EMERYVILLE,CA 94608
关键词
D O I
10.1074/jbc.271.30.17605
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
Insulin stimulation of 3T3-L1 adipocytes causes rapid translocation of actin and the GLUT4 glucose transporter to the plasma membrane, Both processes depend on the activity of phosphatidylinositol 3-kinase, Using single cell microinjection, we have transiently expressed a constitutively activated mutant of phosphatidylinositol 3-kinase, p110*, in 3T3-L1 adipocytes, Fluorescent detection of GLUT4 protein and actin within these cells demonstrates that expression of p110* is sufficient to cause translocation of GLUT4 to the plasma membrane and the formation of actin membrane ruffles, These effects are inhibited by wortmannin in the p110*-expressing cells, indicating that the phosphatidylinositol 3-kinase activity of the protein is required, Overexpression of an identical protein containing a point mutation in the kinase domain, p110*Delta kin, was incapable of mediating either action, confirming that neither the microinjection process nor a nonspecific effect of the protein was responsible for the observed effects, These data suggest that although insulin is capable of inducing numerous signaling pathways, the isolated activation of phosphatidylinositol 3-kinase can initiate the signaling cascade leading to both actin rearrangement and GLUT4 translocation in the absence of insulin stimulation.
引用
收藏
页码:17605 / 17608
页数:4
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