New protein kinase and protein phosphatase families mediate signal transduction in bacterial catabolite repression

^†Institut de Biologie et Chimie des Protéines, Unité Propre de Recherche 412, Centre National de la Recherche Scientifique, F-69367 Lyon Cedex 07, France; ^‡Department of Microbiology, Ruhr-Universität Bochum, NDEF 06, D-44780 Bochum, Germany; and ^¶Laboratoire de Chimie Bactérienne, Unité Propre de Recherche 9043, Centre National de la Recherche Scientifique, F-13009 Marseille, France

Edited by Hans Kornberg, Boston University, Boston, MA, and approved November 25, 1997 (received for review September 12, 1997)

Abstract

Carbon catabolite repression (CCR) is the prototype of a signal transduction mechanism. In enteric bacteria, cAMP was considered to be the second messenger in CCR by playing a role reminiscent of its actions in eukaryotic cells. However, recent results suggest that CCR in Escherichia coli is mediated mainly by an inducer exclusion mechanism. In many Gram-positive bacteria, CCR is triggered by fructose-1,6-bisphosphate, which activates HPr kinase, presumed to be one of the most ancient serine protein kinases. We here report cloning of the Bacillus subtilis hprK and hprP genes and characterization of the encoded HPr kinase and P-Ser-HPr phosphatase. P-Ser-HPr phosphatase forms a new family of phosphatases together with bacterial phosphoglycolate phosphatase, yeast glycerol-3-phosphatase, and 2-deoxyglucose-6-phosphate phosphatase whereas HPr kinase represents a new family of protein kinases on its own. It does not contain the domain structure typical for eukaryotic protein kinases. Although up to now the HPr modifying/demodifying enzymes were thought to exist only in Gram-positive bacteria, a sequence comparison revealed that they also are present in several Gram-negative pathogenic bacteria.

Footnotes

↵ * The first two authors contributed equally to this work.
↵ ‖ Present address: Laboratoire de Génétique des Microorganismes, Institut National de la Recherche Agronomique and Centre National de la Recherche Scientifique, ERS-567, F-78850 Thiverval-Grignon, France.
↵ § To whom reprint requests should be addressed. e-mail: wolfgang.hengstenberg{at}rz.ruhr-uni-bochum.de.
This paper was submitted directly (Track II) to the Proceedings Office.
Abbreviations: CCR, carbon catabolite repression; FBP, fructose 1,6 bisphosphate; HPr, histidine containing HPr; PTS, phosphoenolpyruvate:sugar phosphotransferase system; CcpA, catabolite control protein A; cre, catabolite responsive element; Crh, catabolite repression HPr.