title: Enhanced degradation of stimulatory G-protein (Gs alpha) by cholera toxin is mediated by ADP-ribosylation of Gs alpha protein but not by increased cyclic AMP levels.
abstract: Cholera toxin (CT) catalyses ADP-ribosylation of the alpha-subunit of stimulatory protein (Gs) leading to stimulation of adenylyl cyclase and elevated intracellular cAMP. Persistent treatment (24-48 h) of C6 glioma cells with cholera toxin (100 ng/ml) caused marked downregulation of Gs alpha (75-80%) which could not be mimicked by dibutyryl cAMP (1 mM) and forskolin (10 microM) over the same time periods suggesting that CT-mediated Gs alpha downregulation is independent of cAMP production. However, CT increased the expression of Gq/11 alpha proteins at 24 and 48 h of treatment. The increase in mRNA levels of Gq/11 alpha proteins preceded the increase in Gq/11 proteins. Such stimulatory effects of CT were mimicked by forskolin and dibutyryl-cAMP. These results suggest that CT-mediated downregulation of Gs alpha is independent of cAMP but CT upregulates the expression of Gq/11 alpha proteins in a cAMP-dependent manner.
authors.affiliation: Department of Physiology and Pharmacology, Aga Khan University, Karachi, Pakistan.
authors.forename: B H
authors.initials: BH
authors.lastname: Shah
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D005576:Colforsin; D000246:Adenosine Diphosphate Ribose; D003994:Bucladesine; D002772:Cholera Toxin; D000242:Cyclic AMP; D019205:GTP-Binding Protein alpha Subunits, Gs