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

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Abstract
Disruption of Dictyostelium rasC , encoding a Ras subfamily protein, generated cells incapable of aggregation. While rasC expression is enriched in a cell type‐specific manner during post‐aggregative development, the defect in rasC− cells is restricted to aggregation and fully corrected by application of exogenous cAMP pulses. cAMP is not produced in rasC− cells stimulated by 2′‐deoxy‐cAMP, but is produced in response to GTPγS in cell lysates, indicating that G‐protein‐coupled cAMP receptor activation of adenylyl cyclase is regulated by RasC. However, cAMP‐induced ERK2 phosphorylation is unaffected in rasC− cells, indicating that RasC is not an upstream activator of the mitogen‐activated protein kinase required for cAMP relay. rasC− cells also exhibit reduced chemotaxis to cAMP during early development and delayed response to periodic cAMP stimuli produced by wild‐type cells in chimeric mixtures. Furthermore, cAMP‐induced Akt/PKB phosphorylation through a phosphatidylinositide 3‐kinase (PI3K)‐dependent pathway is dramatically reduced in rasC− cells, suggesting that G‐protein‐coupled serpentine receptor activation of PI3K is regulated by RasC. Cells lacking the RasGEF, AleA, exhibit similar defects as rasC− cells, suggesting that AleA may activate RasC.