cAMP and beta gamma subunits of heterotrimeric G proteins stimulate the mitogen-activated protein kinase pathway in COS-7 cells

• Published in: The Journal of biological chemistry Vol. 269; no. 11; pp. 7851 - 7854
• Main Authors: Faure, M, Voyno-Yasenetskaya, T A, Bourne, H R
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 18.03.1994
• Subjects: Animals; Bombesin - pharmacology; Calcium-Calmodulin-Dependent Protein Kinases - biosynthesis; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Carbachol - pharmacology; Cell Line; Chorionic Gonadotropin - pharmacology; Cricetinae; Cricetulus; Cyclic AMP - metabolism; DNA, Complementary - metabolism; Epidermal Growth Factor - pharmacology; Ergolines - pharmacology; GTP-Binding Proteins - metabolism; Humans; Kinetics; Macromolecular Substances; Mutagenesis; Phenylisopropyladenosine - pharmacology; Phosphatidylinositols - metabolism; Protein Kinase C - biosynthesis; Protein Kinase C - metabolism; Quinpirole; Rats; Receptors, Bombesin - drug effects; Receptors, Bombesin - physiology; Receptors, Dopamine D2 - drug effects; Receptors, Dopamine D2 - physiology; Receptors, LH - drug effects; Receptors, LH - physiology; Receptors, Muscarinic - drug effects; Receptors, Muscarinic - physiology; Receptors, Purinergic P1 - drug effects; Receptors, Purinergic P1 - physiology; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(17)37127-2

Mitogen-activated protein kinases (MAPKs) are activated by a variety of extracellular stimuli, including agonists for G protein-coupled receptors. Using transient transfection of COS-7 cells, we have studied the stimulation of a hemagglutinin-tagged p44mapk (p44HA-mapk) by receptors coupled to Gs, Gq, and Gi. Agonists that act via all three G proteins stimulated p44HA-mapk activity. A constitutively activated alpha s mutant, forskolin, and a cAMP analog also increased p44HA-mapk activity, indicating that cAMP in COS-7 cells, in contrast to other cell types, activates the MAPK pathway. Similarly, a constitutively activated alpha q mutant, overexpression of phospholipase C-beta 2, and a phorbol ester also stimulated p44HA-mapk, suggesting that Gq-coupled receptors stimulate the MAPK pathway by increasing phosphatidylinositol turnover and probably stimulating protein kinase C. In COS-7 cells, in contrast to Rat-1 cells, mutationally activated alpha i did not stimulate the MAPK pathway. G protein beta and gamma subunits, overexpressed together, did activate p44HA-mapk; this finding suggests that in COS-7 cells Gi-coupled receptors may stimulate the MAPK pathway through beta gamma. These unexpected results in COS-7 cells show that G proteins and second messengers regulate the MAPK pathway differently in different cell types.