RasC is required for optimal activation of adenylyl cyclase and Akt/PKB during aggregation

Disruption of Dictyostelium rasC, encoding a Ras subfamily protein, generat ed cells incapable of aggregation. While rasC expression is enriched in a c ell type-specific manner during post-aggregative development, the defect in rasC(-) cells is restricted to aggregation and fully corrected by applicat ion of exogenous cAMP pulses. cAMP is not produced in rasC(-) cells stimula ted by 2 ' -deoxy-cAMP, but is produced in response to GTP gammaS in cell l ysates, indicating that G-protein-coupled cAMP receptor activation of adeny lyl cyclase is regulated by RasC. However, cAMP-induced ERK2 phosphorylatio n is unaffected in rasC(-) cells, indicating that RasC is not an upstream a ctivator of the mitogen-activated protein kinase required for cAMP relay. r asC(-) cells also exhibit reduced chemotaxis to cAMP during early developme nt and delayed response to periodic cAMP stimuli produced by wild-type cell s in chimeric mixtures. Furthermore, cAMP-induced Akt/PKB phosphorylation t hrough a phosphatidylinositide 3-kinase (PI3K)-dependent pathway is dramati cally reduced in rasC(-) cells, suggesting that G-protein-coupled serpentin e receptor activation of PI3K is regulated by RasC. Cells lacking the RasGE F, AleA, exhibit similar defects as rasC(-) cells, suggesting that AleA may activate RasC.