INVOLVEMENT OF PHOSPHOINOSITIDE 3-KINASE IN INSULIN-INDUCED OR IGF-1-INDUCED MEMBRANE RUFFLING
INVOLVEMENT OF PHOSPHOINOSITIDE 3-KINASE IN INSULIN-INDUCED OR IGF-1-INDUCED MEMBRANE RUFFLING
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DOI：
10.1002/j.1460-2075.1994.tb06515.x
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发表时间：
1994-05-15
期刊：
影响因子：
11.4
通讯作者：
KASUGA, M
中科院分区：
文献类型：
--
作者：
KOTANI, K;YONEZAWA, K;KASUGA, M
胰岛素、IGF-1或EGF通过各自的酪氨酸激酶受体诱导膜褶皱。为了阐明受体激活和膜褶皱之间的分子联系，我们将含有YMXM基的磷酸化肽或缺乏pi3激酶110 kDa亚基结合位点的pi3激酶85 kDa突变体（Delta p85）微注射到人表皮样癌KB细胞的细胞质中。两者均抑制无细胞系统中胰岛素受体底物-1 （IRS-1）与PI - 3激酶的关联，并抑制胰岛素或igf -1诱导的KB细胞膜褶皱，但不抑制egf诱导的膜褶皱。微注射非磷酸化类似物、含有EYYE基序的磷酸化肽或野生型85kda亚基（Wp85），在无细胞系统中都不抑制IRS-1与PI 3-激酶的关联，也不抑制KB细胞的膜褶皱。此外，wortmannin，一种PI 3-激酶活性抑制剂，抑制胰岛素或igf -1诱导的膜褶皱。这些结果表明，胰岛素或igf -1诱导的膜褶皱需要IRS-1与PI - 3激酶的关联，随后PI - 3激酶的激活，而不是egf诱导的膜褶皱。
Insulin, IGF-1 or EGF induce membrane ruffling through their respective tyrosine kinase receptors. To elucidate the molecular link between receptor activation and membrane ruffling, we microinjected phosphorylated peptides containing YMXM motifs or a mutant 85 kDa subunit of phosphoinositide (PI) 3-kinase (Delta p85) which lacks a binding site for the catalytic 110 kDa subunit of PI 3-kinase into the cytoplasm of human epidermoid carcinoma KB cells. Both inhibited the association of insulin receptor substrate-1 (IRS-1) with PI 3-kinase in a cell-free system and also inhibited insulin- or IGF-1-induced, but not EGF-induced, membrane ruffling in KB cells. Microinjection of nonphosphorylated analogues, phosphorylated peptides containing the EYYE motif or wild-type 85 kDa subunit (Wp85), all of which did not inhibit the association of IRS-1 with PI 3-kinase in a cell-free system, did not inhibit membrane ruffling in KB cells. In addition, wortmannin, an inhibitor of PI 3-kinase activity, inhibited insulin- or IGF-1-induced membrane ruffling. These results suggest that the association of IRS-1 with PI 3-kinase followed by the activation of PI 3-kinase are required for insulin- or IGF-1-induced, but not for EGF-induced, membrane ruffling.