{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Roelants FM"],"funding":["Biotechnology and Biological Sciences Research Council","NIGMS NIH HHS"],"pagination":["2128-2136"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6232965"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["29(17)"],"pubmed_abstract":["In our proteome-wide screen, Ysp2 (also known as Lam2/Ltc4) was identified as a likely physiologically relevant target of the TOR complex 2 (TORC2)-dependent protein kinase Ypk1 in the yeast Saccharomyces cerevisiae. Ysp2 was subsequently shown to be one of a new family of sterol-binding proteins located at plasma membrane (PM)-endoplasmic reticulum (ER) contact sites. Here we document that Ysp2 and its paralogue Lam4/Ltc3 are authentic Ypk1 substrates in vivo and show using genetic and biochemical criteria that Ypk1-mediated phosphorylation inhibits the ability of these proteins to promote retrograde transport of sterols from the PM to the ER. Furthermore, we provide evidence that a change in PM sterol homeostasis promotes cell survival under membrane-perturbing conditions known to activate TORC2-Ypk1 signaling. These observations define the underlying molecular basis of a new regulatory mechanism for cellular response to plasma membrane stress."],"journal":["Molecular biology of the cell"],"pubmed_title":["TOR complex 2-regulated protein kinase Ypk1 controls sterol distribution by inhibiting StARkin domain-containing proteins located at plasma membrane-endoplasmic reticulum contact sites."],"pmcid":["PMC6232965"],"funding_grant_id":["R01 GM021841","BB/P003818/1","BB/P003818"],"pubmed_authors":["Davis JC","Chauhan N","Muir A","Menon AK","Thorner J","Roelants FM","Levine TP"],"additional_accession":[]},"is_claimable":false,"name":"TOR complex 2-regulated protein kinase Ypk1 controls sterol distribution by inhibiting StARkin domain-containing proteins located at plasma membrane-endoplasmic reticulum contact sites.","description":"In our proteome-wide screen, Ysp2 (also known as Lam2/Ltc4) was identified as a likely physiologically relevant target of the TOR complex 2 (TORC2)-dependent protein kinase Ypk1 in the yeast Saccharomyces cerevisiae. Ysp2 was subsequently shown to be one of a new family of sterol-binding proteins located at plasma membrane (PM)-endoplasmic reticulum (ER) contact sites. Here we document that Ysp2 and its paralogue Lam4/Ltc3 are authentic Ypk1 substrates in vivo and show using genetic and biochemical criteria that Ypk1-mediated phosphorylation inhibits the ability of these proteins to promote retrograde transport of sterols from the PM to the ER. Furthermore, we provide evidence that a change in PM sterol homeostasis promotes cell survival under membrane-perturbing conditions known to activate TORC2-Ypk1 signaling. These observations define the underlying molecular basis of a new regulatory mechanism for cellular response to plasma membrane stress.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Aug","modification":"2022-02-09T10:23:54.245Z","creation":"2019-03-27T00:08:25Z"},"accession":"S-EPMC6232965","cross_references":{"pubmed":["29927351"],"doi":["10.1091/mbc.E18-04-0229"]}}