Cytoskeletal reorganization induced by insulin: involvement of Grb2/Ash, Ras and phosphatidylinositol 3-kinase signalling.
BACKGROUND: Cytoskeletal reorganization is important for a wide variety of insulin-mediated biological actions, including cell growth, migration and metabolism, but the intracellular signalling pathways leading to insulin-induced cytoskeletal reorganization have largely been unknown. We therefore investigated the involvement of Grb2/Ash-Ras and phosphatidylinositol (PI) 3-kinase in the insulin-induced morphological changes in fibroblasts over-expressing human insulin receptors (HIRcB cells). RESULTS: Insulin, as well as 12-O-tetradecanoylphorbol-13-acetate (TPA) and 8-bromo-cAMP, induced a unique morphological change associated with actin cytoskeletal reorganization characterized by the disruption of actin stress fibres and thicker actin bundle formation. Microinjection of an anti-Grb2/Ash antibody, but not control IgG, inhibited the insulin-induced actin reorganization, whereas the TPA- and 8-bromo-cAMP-induced morphological changes were not inhibited by microinjection of the anti-Grb2/Ash antibody. In addition, microinjection of dominant negative ras p21 protein, but not the heat-treated protein, inhibited insulin-induced cytoskeletal reorganization. Microinjection of activated p21ras protein resulted in very similar cytoskeletal reorganization with actin bundle formation in the cytoplasm. The PI3-kinase inhibitor wortmannin inhibited insulin-induced cytoskeletal reorganization, but not the TPA- nor 8-bromo-cAMP-induced reorganization. Interestingly, wortmannin also inhibited the activated p21ras-induced morphological change. CONCLUSIONS: We concluded that Grb2/Ash-Ras activation and probably Ras- associated PI3-kinase activation are involved in the insulin-induced morphological change.[1]References
- Cytoskeletal reorganization induced by insulin: involvement of Grb2/Ash, Ras and phosphatidylinositol 3-kinase signalling. Tobe, K., Asai, S., Matuoka, K., Yamamoto, T., Chida, K., Kaburagi, Y., Akanuma, Y., Kuroki, T., Takenawa, T., Kimura, S., Nagai, R., Kadowaki, T. Genes Cells (2003) [Pubmed]
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