Temperature-sensitive Gbeta mutants discriminate between G protein-dependent and -independent signaling mediated by serpentine receptors.
Deletion of the single gene for the Dictyostelium G protein beta-subunit blocks development at an early stage. We have now isolated temperature-sensitive alleles of Gbeta to investigate its role in later development. We show that Gbeta is directly required for adenylyl cyclase A activation and for morphogenetic signaling during the entire developmental program. Gbeta was also essential for induction of aggregative gene expression by cAMP pulses, a process that is mediated by serpentine cAMP receptors (cARs). However, Gbeta was not required for cAR-mediated induction of prespore genes and repression of stalk genes, and neither was Gbeta needed for induction of prestalk genes by the differentiation inducing factor (DIF). cAMP induction of prespore genes and repression of stalk genes is mediated by the protein kinase GSK-3. GSK-3 also determines cell-type specification in insects and vertebrates and is regulated by the wingless/wnt morphogens that are detected by serpentine fz receptors. The G protein-dependent and -independent modes of cAR-mediated signaling reported here may also exist for the wingless/wnt signaling pathways in higher organisms.
Department of Biological Chemistry, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
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Soede
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D000262:Adenylyl Cyclases / Q000378:metabolism; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D000242:Cyclic AMP / Q000494:pharmacology; D004023:Dictyostelium / Q000166:cytology / Q000235:genetics*; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3; D006358:Hot Temperature; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009154:Mutation; D011953:Receptors, Cyclic AMP / Q000378:metabolism*; D012641:Selection, Genetic; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D011953:Receptors, Cyclic AMP; D000242:Cyclic AMP; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases