title: Chemoattractant-mediated increases in cGMP induce changes in Dictyostelium myosin II heavy chain-specific protein kinase C activities.
abstract: Myosin II heavy chain (MHC)-specific protein kinase C (MHC-PKC) isolated from the ameba, Dictyostelium discoideum, regulates myosin II assembly and localization in response to the chemoattractant cAMP (Abu-Elneel et al. 1996. J. Biol. Chem. 271:977- 984). Recent studies have indicated that cAMP-induced cGMP accumulation plays a role in the regulation of myosin II phosphorylation and localization (Liu, G., and P. Newell. 1991. J. Cell. Sci. 98: 483-490). This report describes the roles of cAMP and cGMP in the regulation of MHC-PKC membrane association, phosphorylation, and activity (hereafter termed MHC-PKC activities). cAMP stimulation of Dictyostelium cells resulted in translocation of MHC-PKC from the cytosol to the membrane fraction, as well as increasing in MHC-PKC phosphorylation and in its kinase activity. We present evidence that MHC is phosphorylated by MHC-PKC in the cell cortex which leads to myosin II dissociation from the cytoskeleton. Use of Dictyostelium mutants that exhibit aberrant cAMP-induced increases in cGMP accumulation revealed that MHC-PKC activities are regulated by cGMP. Dictyostelium streamer F mutant (stmF), which produces a prolonged peak of cGMP accumulation upon cAMP stimulation, exhibits prolonged increases in MHC-PKC activities. In contrast, Dictyostelium KI-10 mutant that lacks the normal cAMP-induced cGMP response, or KI-4 mutant that shows nearly normal cAMP-induced cGMP response but has aberrant cGMP binding activity, show no changes in MHC-PKC activities. We provide evidence that cGMP may affect MHC-PKC activities via the activation of cGMP-dependent protein kinase which, in turn, phosphorylates MHC-PKC. The results presented here indicate that cAMP-induced cGMP accumulation regulates myosin II phosphorylation and localization via the regulation of MHC-PKC.
authors.affiliation: Department of Biochemistry, Hadassah Medical School, Hebrew University, Jerusalem, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Dembinsky
authors.forename: H
authors.initials: H
authors.lastname: Rubin
authors.forename: S
authors.initials: S
authors.lastname: Ravid
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002227:Carbazoles; D002462:Cell Membrane / Q000201:enzymology; D002630:Chemotactic Factors / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology* / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D003599:Cytoskeleton / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D004023:Dictyostelium / Q000201:enzymology* / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles; D007700:Kinetics; D009154:Mutation; D018995:Myosin Heavy Chains / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism; D010766:Phosphorylation; D015800:Protozoan Proteins
chemical_list: D000470:Alkaloids; D002227:Carbazoles; D002630:Chemotactic Factors; D004791:Enzyme Inhibitors; D007211:Indoles; D015800:Protozoan Proteins; C073601:KT 5823; D000242:Cyclic AMP; D017869:Cyclic GMP-Dependent Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C033142:myosin-heavy-chain kinase; D018995:Myosin Heavy Chains; D009218:Myosins; D006152:Cyclic GMP