Phosphorylation of chemoattractant receptors is not essential for chemotaxis or termination of G-protein-mediated responses.
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 of Dictyostelium, 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 did not 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.
Kim
J Y
JY
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Soede
R D
RD
Schaap
P
P
Valkema
R
R
Borleis
J A
JA
Van Haastert
P J
PJ
Devreotes
P N
PN
Hereld
D
D
D000199:Actins / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D019943:Amino Acid Substitution; D000818:Animals; D002449:Cell Aggregation; D002454:Cell Differentiation; D002633:Chemotaxis; D004023:Dictyostelium / Q000502:physiology*; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000378:metabolism; D007700:Kinetics; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011953:Receptors, Cyclic AMP / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D017384:Sequence Deletion; D012694:Serine
D000199:Actins; D011953:Receptors, Cyclic AMP; D011994:Recombinant Proteins; D012694:Serine; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase