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Originally published In Press as doi:10.1074/jbc.M203515200 on June 21, 2002

J. Biol. Chem., Vol. 277, Issue 36, 33468-33476, September 6, 2002
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Sit4 Is Required for Proper Modulation of the Biological Functions Mediated by Pkc1 and the Cell Integrity Pathway in Saccharomyces cerevisiae*

Maria Angeles de la Torre-RuizDagger §, Jordi TorresDagger §, Joaquin Ariño||, and Enrique HerreroDagger

From the Dagger  Departament de Ciències Mèdiques Bàsiques, Facultat de Medicina, Universitat de Lleida, Rovira Roure 44, 25198-Lleida, Spain and the || Departament de Bioquimica i Biologia Molecular, Facultat de Veterinaria, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona, Spain

Maintenance of cellular integrity in Saccharomyces cerevisiae is carried out by the activation of the protein kinase C-mediated mitogen-activated protein kinase (PKC1-MAPK) pathway. Here we report that correct down-regulation of both basal and induced activity of the PKC1-MAPK pathway requires the SIT4 function. Sit4 is a protein phosphatase also required for a proper cell cycle progression. We present evidence demonstrating that the G1 to S delay in the cell cycle, which occurs as a consequence of the absence of Sit4, is mediated by up-regulation of Pkc1 activity. Sit4 operates downstream of the plasma membrane sensors Mid2, Wsc1, and Wsc2 and upstream of Pkc1. Sit4 affects all known biological functions involving Pkc1, namely Mpk1 activity and cell wall integrity, actin cytoskeleton organization, and ribosomal gene transcription.

* This work was supported by Grants SGR99/00/70 from Generalilat de Catalunya and PB97-1456 from Ministerio de Educación y Cultura (to E. H.) and PB98-0565-C4-02 from Ministerio de Educación y Cultura (to J. A.), a Spanish Ministerio de Educación y Cultura postdoctoral contract (to M. A. T. R.), and a Generalitat de Catalunya fellowship (to J. T. R.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Both authors contributed equally to this work.

To whom correspondence should be addressed. E-mail: madelatorre@cmb.udl.es.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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