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| The EMBO Journal
(1998) 17, 2838–2845, doi:10.1093/emboj/17.10.2838 |
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| An intersection of the cAMP/PKA and two-component signal transduction systems in Dictyostelium |
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| Peter A. Thomason1, 5, David Traynor1, 5, Guy Cavet2, Wen-Tsan Chang3, Adrian J. Harwood4 and Robert R. Kay1 |
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1 MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK 2 Present address: Biochemistry Department, B407, Beckman Center, Stanford University Medical Center, Stanford, CA 94305, USA 3 Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK 4 Present address: MRC Laboratory for Molecular Cell Biology, University College London, Gower St, London WC1E 6BT, UK 5 P.A.Thomason and D.Traynor contributed equally to this work To whom correspondence should be addressed Robert R. Kay, rrk@mrc-lmb.cam.ac.uk Received 26 January 1998; Revised 6 March 1998; Accepted 11 March 1998. |
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| Abstract |
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Terminal differentiation of both stalk and spore cells in Dictyostelium can be triggered by activation of cAMP-dependent protein kinase (PKA). A screen for mutants where stalk and spore cells mature in isolation produced three genes which may act as negative regulators of PKA: rdeC (encoding the PKA regulatory subunit), regA and rdeA. The biochemical properties of RegA were studied in detail. One domain is a cAMP phosphodiesterase (Km  5  M); the other is homologous to response regulators (RRs) of two-component signal transduction systems. It can accept phosphate from acetyl phosphate in a reaction typical of RRs, with transfer dependent on Asp212, the predicted phosphoacceptor. RegA phosphodiesterase activity is stimulated up to 8-fold by the phosphodonor phosphoramidate, with stimulation again dependent on Asp212. This indicates that phosphorylation of the RR domain activates the phosphodiesterase domain. Overexpression of the RR domain in wild-type cells phenocopies a regA null. We interpret this dominant-negative effect as due to a diversion of the normal flow of phosphates from RegA, thus preventing its activation. Mutation of rdeA is known to produce elevated cAMP levels. We propose that cAMP breakdown is controlled by a phosphorelay system which activates RegA, and may include RdeA. Cell maturation should be triggered when this system is inhibited. |
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| Keywords: Dictyostelium, phosphorelay, protein kinase A, RegA, response regulator |
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