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J. Biol. Chem., Vol. 281, Issue 36, 26144-26149, September 8, 2006
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1
From the
Mississippi Functional Genomics Network (MFGN), Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, Mississippi 39406 and the
Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110
The yeast Saccharomyces cerevisiae deploys two different types of glucose sensors on its cell surface that operate in distinct glucose signaling pathways: the glucose transporter-like Snf3 and Rgt2 proteins and the Gpr1 receptor that is coupled to Gpa2, a G-protein
subunit. The ultimate target of the Snf3/Rgt2 pathway is Rgt1, a transcription factor that regulates expression of HXT genes encoding glucose transporters. We have found that the cAMP-dependent protein kinase A (PKA), which is activated by the Gpr1/Gpa2 glucose-sensing pathway and by a glucose-sensing pathway that works through Ras1 and Ras2, catalyzes phosphorylation of Rgt1 and regulates its function. Rgt1 is phosphorylated in vitro by all three isoforms of PKA, and this requires several serine residues located in PKA consensus sequences within Rgt1. PKA and the consensus serine residues of Rgt1 are required for glucose-induced removal of Rgt1 from the HXT promoters and for induction of HXT expression. Conversely, overexpression of the TPK genes led to constitutive expression of the HXT genes. The PKA consensus phosphorylation sites of Rgt1 are required for an intramolecular interaction that is thought to regulate its DNA binding activity. Thus, two different glucose signal transduction pathways converge on Rgt1 to regulate expression of glucose transporters.
Received for publication, April 14, 2006 , and in revised form, June 7, 2006.
* This work was supported by National Institutes of Health Grant GM32540 (to M. J.) and National Institutes of Health Grant RR016476-04 from the MS INBRE Program of the National Center for Research Resources. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 To whom correspondence should be addressed: MFGN, Dept. of Biological Sciences, University of Southern Mississippi, 118 College Dr. #5018, Hattiesburg, MS 39406. Tel.: 601-266-4262; Fax: 601-266-5068; E-mail: jeongho.kim{at}mfgn.usm.edu.
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