Seven Helix Chemoattractant Receptors Transiently Stimulate Mitogen-activated Protein Kinase in Dictyostelium

doi:10.1074/jbc.271.7.3351

Seven Helix Chemoattractant Receptors Transiently Stimulate Mitogen-activated Protein Kinase in Dictyostelium

ROLE OF HETEROTRIMERIC G PROTEINS (*)

From the (1)Department of Biology, Center for Molecular Genetics, University of California, San Diego, La Jolla, California 92093-0634 and the
(2)Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

^§§To whom correspondence should be addressed:
Center for Molecular Genetics, Rm. 225, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0634.
Tel.: 619-534-2788; Fax: 619-534-7073; :rafirtel{at}ucsd.edu.

↵^§ Supported in part by the Ministry of Education, Science, and Culture of Japan(06044234). Present address: Dept. of Biology, Faculty of Science, Osaka University, Toyonaka, Osaka 560, Japan.
↵** Present address: MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom.

Abstract

Mitogen-activated protein (MAP) kinases are involved in controlling a cell's responses to a variety of stimuli and can be activated by both protein tyrosine kinase and G protein-coupled receptors. It was shown previously that Dictyostelium MAP kinase ERK2 is required for normal activation of adenylyl cyclase and erk2 null cells are aggregation-deficient. In this manuscript, we show that the Dictyostelium MAP kinase ERK2 is rapidly and transiently activated in response to the chemoattractant cAMP. This response requires cAMP receptors, but is independent of the coupled Gα2 subunit and the only known Gβ subunit. These data indicate that ligand-mediated receptor activation of adenylyl cyclase requires two receptor-dependent pathways, one of which requires heterotrimeric G proteins, including Gα2 and the only known Gβ subunit, and the second of which requires ERK2. Our results suggest that ERK2 may be activated by a novel receptor-mediated pathway.

Footnotes

↵^¶ Supported by a “Fondation pour la Recherche Medicale de France” fellowship.
↵* This work was supported by United States Public Health Service Grants GM28007 (to P. N. D.) and GM37830 (to R. A. F.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹

MAP

mitogen-activated protein

MAPK

mitogen-activated protein kinase

MES

4-morpholineethanesulfonic acid

MBA

myelin basic protein

PBS

phosphate-buffered saline

GST

glutathione S-transferase

GTPS

guanosine 5′-O-(3-thiotriphosphate)

cAR

cAMP receptors.
- Received December 6, 1995.
- Revision received December 22, 1995.