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J. Biol. Chem., Vol. 278, Issue 51, 51441-51447, December 19, 2003

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Insight into Functional Aspects of Stt3p, a Subunit of the Oligosaccharyl Transferase

EVIDENCE FOR INTERACTION OF THE N-TERMINAL DOMAIN OF Stt3p WITH THE PROTEIN KINASE C CASCADE^*

Manasi Chavan, Magdalena Rekowicz, and William Lennarz

From the Department of Biochemistry and Cell Biology, State University of New York, Stony Brook, New York 11794

Over a decade ago, the gene STT3 was identified in a staurosporine and temperature sensitivity screen of yeast. Subsequently the product of this gene was shown to be a subunit of the endoplasmic reticulum-localized oligosaccharyl transferase (OT) complex. Although stt3 mutants are known to be staurosporine-sensitive, we found that mutants of other OT subunits (except ost4) are staurosporine-resistant, which indicates that this phenotype of stt3 mutants is not simply a consequence of their defect in glycosylation, as previously speculated. Staurosporine sensitivity was found to be an allele-specific phenotype restricted to cells harboring mutations in highly conserved residues in the N-terminal domain of the STT3 protein. Cells bearing mutations in one of the cytosolic-oriented loops (amino acids 158-168) in the N terminus of Stt3p were found to be specifically susceptible to staurosporine. Staurosporine is a specific inhibitor of Pkc1p, and a genetic link had previously been suggested between PKC1 and STT3. It is known that overexpression of PKC1 suppresses the staurosporine sensitivity of the stt3 mutants in an allele-specific manner, which is typical of mutants of Pkc1p cascade. It has been shown that the pkc1 null mutant exhibits lowered OT activity. Our results combined with these previous observations indicate that the N-terminal domain of Stt3p may interact with members of the Pkc1p cascade and consequently mutations in this domain result in staurosporine sensitivity. We further speculate that the Pkc1p regulates OT activity through the N-terminal domain of Stt3p, the C-terminal domain of which possesses the recognition and/or catalytic site of the OT complex.

Received for publication, September 22, 2003 , and in revised form, October 3, 2003.

^* This work was supported by National Institutes of Health Grant GM33185 (to W. L.). 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.

To whom correspondence should be addressed: Dept. of Biochemistry and Cell Biology, 450A, Life Science Bldg., SUNY, Stony Brook, NY 11794. Tel.: 631-632-8550; Fax: 631-632-8575; E-mail: wlennarz{at}notes.cc.sunysb.edu.

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