What does insulin do to Ras?

The Ras pathway lies in the center of signalling cascades of numerous growth-promoting factors. The Ras pathway appears to connect signalling events that begin at the plasma membrane with nuclear events. Insulin is one of the major stimulants of the Ras signalling pathway. The influence of insulin on this pathway consists of five important events: (1) p21Ras activation is promoted by insulin stimulation of the guanine nucleotide exchange factor, Sos, resulting in increased GTP-loading of p21Ras; (2) p21Ras deactivation involves the hyperphosphorylation of Sos; (3) insulin increases farnesyltransferase (FTase) activity that farnesylates p21Ras; (4) increased amounts of farnesylated p21Ras translocate to the plasma membrane where they can be activated by other growth-promoting agents; and (5) cellular responses to other growth factors are potentiated by insulin-stimulated pre-loading of the plasma membrane with farnesylated p21Ras. Published by Elsevier Science Inc.