RRC ID 29032
Author Lim CJ, Spiegelman GB, Weeks G.
Title RasC is required for optimal activation of adenylyl cyclase and Akt/PKB during aggregation.
Journal EMBO J
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 GTPgammaS 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.
Volume 20(16)
Pages 4490-9
Published 2001-8-15
DOI 10.1093/emboj/20.16.4490
PMID 11500376
PMC PMC125575
MeSH Adenylyl Cyclases / metabolism* Animals Chemotaxis Cyclic AMP / metabolism Dictyostelium / cytology Dictyostelium / metabolism Dictyostelium / physiology Enzyme Activation Fungal Proteins* Mitogen-Activated Protein Kinase 1 / metabolism Mutagenesis Phenotype Phosphatidylinositol 3-Kinases / metabolism Phosphorylation Protein-Serine-Threonine Kinases* Proto-Oncogene Proteins / metabolism* Proto-Oncogene Proteins c-akt Receptors, Cyclic AMP / metabolism Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism ras Proteins / genetics ras Proteins / metabolism*
IF 9.889
Times Cited 67
Cellular slime molds S00342