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PMID: 11500376 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 20 ·No. 16 ·2001-08-15 ·Pages 4490-9

Lim CJ, Spiegelman GB, Weeks G

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.

MeSH Terms
Adenylyl Cyclases/metabolism Animals Chemotaxis Cyclic AMP/metabolism Dictyostelium/cytology,metabolism,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,metabolism ras Proteins/genetics,metabolism
Chemicals
Fungal Proteins Proto-Oncogene Proteins Receptors, Cyclic AMP Recombinant Fusion Proteins ras protein, Dictyostelium Cyclic AMP Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-akt Mitogen-Activated Protein Kinase 1 ras Proteins Adenylyl Cyclases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lim C J
Department of Microbiology and Immunology and Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
Spiegelman G B
Weeks G
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/20.16.4490
Published
2001-08-15
Pages
4490-9
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125575
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/20.16.4490 PMC Full Text View journal details
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