Phosphorylation of Chemoattractant Receptors Is Not Essential for Chemotaxis or Termination of G-protein-mediated Responses*
- Ji-Yun Kim‡,
- Ron D. M. Soede§,
- Pauline Schaap§,
- Romi Valkema¶,
- Jane A. Borleis‡,
- Peter J. M. Van Haastert¶,
- Peter N. Devreotes‡ and
- Dale Hereld‡‖
- From the ‡Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; §Institute for Molecular Plant Sciences, University of Leiden, Leiden, The Netherlands; and the¶Department of Biochemistry, University of Groningen, Groningen, The Netherlands
Abstract
In several G-protein-coupled signaling systems, ligand-induced receptor phosphorylation by specific kinases is suggested to lead to desensitization via mechanisms including receptor/G-protein uncoupling, receptor internalization, and receptor down-regulation. We report here that elimination of phosphorylation of a chemoattractant receptor ofDictyostelium, either by site-directed substitution of the serines or by truncation of the C-terminal cytoplasmic domain, completely prevented agonist-induced loss of ligand binding but didnot impair the adaptation of several receptor-mediated responses including the activation of adenylyl and guanylyl cyclases and actin polymerization. In addition, the phosphorylation-deficient receptors were capable of mediating chemotaxis, aggregation, and differentiation. We propose that for chemoattractant receptors agonist-induced phosphorylation regulates surface binding activity but other phosphorylation-independent mechanisms mediate response adaptation.
Footnotes
-
↵* This work was supported in part by NIH Grant GM34933 (to P. N. D.) and by American Heart Association Grant 9630188N (to D. H.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵‖ Present address: Dept. of Microbiology and Molecular Genetics, The University of Texas Health Science Ctr., P. O. Box 20708, Houston, TX 77225. Tel.: 713-500-5444; Fax: 713-500-5499; E-mail:dhereld{at}utmmg.med.uth.tmc.edu. To whom correspondence should be addressed.
-
↵1 The abbreviations used are: G-protein, guanine nucleotide-binding regulatory protein; cAR, cAMP receptor; CHAPS, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid; DTT, dithiothreitol; Pipes, 1,4-piperazinediethanesulfonic acid; TRITC, tetramethylrhodamine isothiocyanate.
-
- Received April 21, 1997.
- Revision received August 11, 1997.
