REGULATION OF CELL-PROLIFERATION BY G-PROTEINS

G Proteins provide signal transduction mechanisms to seven transmembra ne receptors. Recent studies have indicated that the alpha-subunits as well as the beta gamma-subunits of these proteins regulate several cr itical signaling pathways involved in cell proliferation, differentiat ion and apoptosis. Of the 17 alpha-subunits that have been cloned, at least ten of them have been shown to couple mitogenic signaling in fib roblast cells. Activating mutations in G alpha(s), G alpha(12), and G alpha(12) have been correlated with different types of tumors. In addi tion, the ability of the beta gamma-subunits to activate mitogenic pat hways in different cell-types has been defined. The present review bri efly summarizes the diverse and novel signaling pathways regulated by the alpha- as well as the beta gamma-subunits of G proteins in regulat ing cell proliferation.