Regulation of guanylate cyclase activity by atrial natriuretic factor and protein kinase C |
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Authors: | Teresa Duda Rameshwar K Sharma |
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Institution: | (1) Section of Regulatory Biology, Department of Brain and Vascular Research, The Cleveland Clinic Research Institute, 9500 Euclid Avenue, 44195-5068 Cleveland, Ohio, USA |
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Abstract: | Summary The putative second messenger of certain atrial natriuretic factor (ANF) signal transductions is cyclic GMP. Recently, we purified a 180-kDa protein, apparently containing both ANF receptor and guanylate cyclase activities, and hypothesized that this is one of the cyclic GMP transmembrane signal transducers. The enzyme is ubiquitous and appears to be conserved. Utilizing the 180-kDa membrane guanylate cyclase, we now show that the 180-kDa guanylate cyclase is regulated in opposing fashions by two receptor signals—ANF stimulating it and protein kinase C inhibiting it. Furthermore, protein kinase C phosphorylates the 180-kDa enzyme. This suggests a novel switch on and switch off mechanism of the cyclic GMP signal transduction. Switch off represents the phosphorylation while switch on the dephosphorylation of the enzyme. |
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Keywords: | atrial natriuretic factor receptor membrane guanylate cyclase protein kinase C phosphorylation |
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