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KMID : 0603519990040020093
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Journal of Korean Association of Cancer Prevention
1999 Volume.4 No. 2 p.93 ~ p.101
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Cellular Function of Rac1 in the Insulin Signal Transduction Pathway
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Yi Ji-Young
Yi Sun-Ju
Kim Kyung-Hwan
Choi Ji-Eun
Jhun Byung-Hak
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Abstract
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We examined a functional role of Rac1 protein in the signal transduction pathway of insulin leading to cell cycle progression in Rat-1 fibroblasts expressing human insulin receptors (HIRc-B). Following microinjection with dominant-negative and oncogenic mutants of Rac1 (Rac1N17) and Ras (RasN17), DNA synthesis in the injected cells was quantitatively analyzed. Rac1N17 and RasN17 inhibited DNA synthesis and membrane ruffling induced by insulin. Maximum inhibition of DNA synthesis by Rac1N17 was less than RasN17. This differential effect of Rac1 and Ras in the mitogenic signaling pathway was confirmed by microinjection of oncogenic Rac1N12 and RasV12. MEK inhibitor, PD98095, inhibited RasV12-induced DNA synthesis, but not Rac1V12-induced DNA synthesis. The co-injection of inhibitory Rac1N17 with RasV12 inhibited RasV12-induced DNA synthesis, but co-injection of oncogenic Rac1V12 with Rac1N17 rescued Rac1N17 blockade. These results suggest that Rac1 protein plays an important role in mitogenic signal transduction pathway of insulin, and that Rac1 and Ras are differentially involved in the pathway.
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KEYWORD
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Rac1, Ras, Mitogenesis, Insulin, Microinjection
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