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A more recent version of this article appeared on February 1, 2005 Originally published as MBC in Press, 10.1091/mbc.E04-07-0549 on December 1, 2004
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Submitted on July 4, 2004
Revised on October 28, 2004
Accepted on November 11, 2004
Department of Cell & Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; *Graduate Program in Pharmacology, Weill Medical College of Cornell University, New York, NY 10021
Monitoring Editor: Keith Mostov
Kin1 and Kin2 are S. cerevisiae counterparts of Par-1, the C. elegans kinase essential for the establishment of polarity in the one cell embryo. Here, we present evidence for a novel link between Kin1, Kin2 and the secretory machinery of the budding yeast. We isolated KIN1 and KIN2 as suppressors of a mutant form of Rho3, a Rho-GTPase acting in polarized trafficking. Genetic analysis suggests that KIN1 and KIN2 act downstream of the Rab-GTPase Sec4, its exchange factor Sec2, and several components of the vesicle tethering complex, the Exocyst. We show that Kin1 and Kin2 physically interact with the t-SNARE Sec9 and the Lgl homologue Sro7, proteins acting at the final stage of exocytosis. Structural analysis of Kin2 reveals that its catalytic activity is essential for its function in the secretory pathway, and implicates the conserved 42 amino acid tail at the carboxy-terminal of the kinase in auto-inhibition. Finally, we find that Kin1 and Kin2 induce phosphorylation of t-SNARE Sec9 in vivo and stimulate its release from the plasma membrane. In summary, we report the finding that yeast Par-1 counterparts are associated with and regulate the function of the exocytic apparatus via phosphorylation of Sec9.
These authors contributed equally to this work.
Corresponding author.
E-mail: pjbrennw{at}med.unc.edu
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