Insulin stimulates the tyrosine phosphorylation of caveolin.
Insulin stimulates the tyrosine phosphorylation of caveolin.
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DOI：
10.1083/jcb.129.6.1523
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发表时间：
1995-06
期刊：
影响因子：
--
通讯作者：
Saltiel AR
中科院分区：
文献类型：
--
作者：
Mastick CC;Brady MJ;Saltiel AR
被称为小窝的特化质膜结构和小窝-外壳蛋白小窝蛋白在胰岛素敏感细胞如脂肪细胞和肌肉中高度表达。用胰岛素刺激3 T3-L1脂肪细胞显著增加了小窝蛋白和富含小窝蛋白的Triton不溶性复合物中29 kD小窝蛋白相关蛋白的酪氨酸磷酸化。最大的磷酸化发生在5分钟内，磷酸化的水平保持升高至少30分钟。胰岛素剂量反应的酪氨酸磷酸化的小窝蛋白和29 kD的小窝蛋白相关蛋白的磷酸化的胰岛素受体。小窝蛋白酪氨酸磷酸化的刺激对胰岛素是特异性的，而在PDGF或EGF中没有观察到，尽管PDGF刺激了29-kD小窝蛋白相关蛋白的酪氨酸磷酸化。增加的酪氨酸磷酸化的小窝蛋白，其相关的29-kD蛋白，和60-kD的蛋白质，观察到在体外激酶测定后，孵育的小窝蛋白富集的Triton不溶性复合物与Mg-ATP，这表明存在的内在酪氨酸激酶在这些复合物。这些组分仅含有痕量的活化胰岛素受体。此外，这些复合物含有在原位凝胶激酶测定中检测到的60 kD激酶和与针对Src家族激酶p59 Fyn的抗体交叉反应的约60 kD蛋白。因此，小窝蛋白的胰岛素依赖性酪氨酸磷酸化代表了一种新的胰岛素特异性信号转导途径，其可能涉及胰岛素受体下游酪氨酸激酶的活化。
The specialized plasma membrane structures termed caveolae and the caveolar-coat protein caveolin are highly expressed in insulin- sensitive cells such as adipocytes and muscle. Stimulation of 3T3-L1 adipocytes with insulin significantly increased the tyrosine phosphorylation of caveolin and a 29-kD caveolin-associated protein in caveolin-enriched Triton-insoluble complexes. Maximal phosphorylation occurred within 5 min, and the levels of phosphorylation remained elevated for at least 30 min. The insulin-dose responses for the tyrosine phosphorylation of caveolin and the 29-kD caveolin-associated protein paralleled those for the phosphorylation of the insulin receptor. The stimulation of caveolin tyrosine phosphorylation was specific for insulin and was not observed with PDGF or EGF, although PDGF stimulated the tyrosine phosphorylation of the 29-kD caveolin- associated protein. Increased tyrosine phosphorylation of caveolin, its associated 29-kD protein, and a 60-kD protein was observed in an in vitro kinase assay after incubation of the caveolin-enriched Triton- insoluble complexes with Mg-ATP, suggesting the presence of an intrinsic tyrosine kinase in these complexes. These fractions contain only trace amounts of the activated insulin receptor. In addition, these complexes contain a 60-kD kinase detected in an in situ gel kinase assay and an approximately 60 kD protein that cross-reacts with an antibody against the Src-family kinase p59Fyn. Thus, the insulin- dependent tyrosine phosphorylation of caveolin represents a novel, insulin-specific signal transduction pathway that may involve activation of a tyrosine kinase downstream of the insulin receptor.