THE TIMING OF INSULIN C-RAS SIGNAL IS CRITICAL FOR ITS EFFECT UPON THE DIFFERENTIATION OF C3H10T1/2-DERIVED PREADIPOCYTES/

The effect of the peptide hormone insulin upon the differentiation of a 10T1/2-derived preadipocytic line was found to display a potent time -dependence. Insulin addition before cell confluence strongly enhanced differentiation, while addition after confluence had no effect. In ke eping with the role of c-Ras as a downstream effector of insulin, c-ra s downregulation before confluence abolished differentiation, while it was ineffective once the process of differentiation was underway. The se data suggest that the insulin signal is effective during an early w indow of time before cell confluence, while normal c-Ras levels are re quired for its transmission. (C) 1997 Elsevier Science Ireland Ltd.