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| Subject Categories: Cell & Tissue Architecture | Signal Transduction |
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| The EMBO Journal
(2004) 23, 3747–3757, doi:10.1038/sj.emboj.7600384 Published online 16 September 2004 |
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| Genome-wide lethality screen identifies new PI4,5P2 effectors that regulate the actin cytoskeleton |
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| Anjon Audhya1, 7, Robbie Loewith2, Ainslie B Parsons3, 4, Lu Gao5, 6, Mitsuaki Tabuchi1, Huilin Zhou5, 6, Charles Boone3, 4, Michael N Hall2 and Scott D Emr1 |
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1 Department of Cellular and Molecular Medicine, The Howard Hughes Medical Institute, University of California, San Diego School of Medicine, La Jolla, CA, USA 2 Division of Biochemistry, Biozentrum, University of Basel, Basel, Switzerland 3 Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada 4 Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada 5 Ludwig Institute for Cancer Research, La Jolla, CA, USA 6 Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA To whom correspondence should be addressed Scott D Emr, Division of Cellular and Molecular Medicine, HHMI, UCSD School of Medicine, Cellular and Molecular Medicine Bldg, Rm 318, 9500 Gilman Drive, 3rd Floor, La Jolla, CA 92093-0668, USA. Tel.: +1 858 534 6462; Fax: +1 858 534 6414; E-mail: semr@ucsd.edu 7 Present address: Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA Received 11 May 2004; Accepted 5 August 2004; Published online 16 September 2004. |
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| Abstract |
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| To further understand the roles played by the essential phosphoinositide PI4,5P2, we have used a synthetic lethal analysis, which systematically combined the mss4ts mutation, partially defective in PI4P 5-kinase activity, with each of approximately 4700 deletion mutations. This genomic screening technique uncovered numerous new candidate effectors and regulators of PI4,5P2 in yeast. In particular, we identified Slm1 (Yil105c), a previously uncharacterized PI4,5P2 binding protein. Like Mss4, Slm1 and its homolog Slm2 (Ynl047c) were required for actin cytoskeleton polarization and viability. Co-immunoprecipitation experiments revealed that Slm1 interacts with a component of TORC2, a Tor2 kinase-containing complex, which also regulates the actin cytoskeleton. Consistent with these findings, phosphorylation of Slm1 and Slm2 was dependent on TORC2 protein kinase activity, both in vivo and in vitro, and Slm1 localization required both PI4,5P2 and functional TORC2. Together, these data suggest that Slm1 and Slm2 function downstream of PI4,5P2 and the TORC2 kinase pathway to control actin cytoskeleton organization. |
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| Keywords: actin, phosphoinositide, polarity, Rho GTPase, TOR |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHIs the nitric oxide system involved in genetic hypertension in Dahl rats? Kidney International Original Article Function of human renin proximal promoter DNA Kidney International Original Article Exo70 interacts with phospholipids and mediates the targeting of the exocyst to the plasma membrane The EMBO Journal Article (19 Sep 2007) Regulation of PI4,5P 2 synthesis by nuclear?cytoplasmic shuttling of the Mss4 lipid kinase The EMBO Journal Article (15 Aug 2003) |
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