ArticleProceedings of the National Academy of Sciences of the United States of America2012
Plasma membrane recruitment and activation of the AGC kinase Ypk1 is mediated by target of rapamycin complex 2 (TORC2) and its effector proteins Slm1 and Slm2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 140 citations in OpenAlex.
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- Uncoupling of nutrient sensing and cell size control by specific defects in ceramide structure.Biology open · 2026Article
- A MAP kinase cascade modulates expression of late G1 phase cyclins in budding yeast.bioRxiv : the preprint server for biology · 2025Article
- Time-resolved monitoring of yeast responses to lipopolysaccharide exposure by cell-released volatile organic compounds.Applied and environmental microbiology · 2025Article
- Making PI3K superfamily enzymes run faster.Advances in biological regulation · 2025Review
- Casein kinase 1 controls components of a TORC2 signaling network in budding yeast.Journal of cell science · 2024Article
- Cell growth and nutrient availability control the mitotic exit signaling network in budding yeast.The Journal of cell biology · 2024Article
- Activation of the cell wall integrity pathway negatively regulates TORC2-Ypk1/2 signaling through blocking eisosome disassembly in Saccharomyces cerevisiae.Communications biology · 2024Article
- Casein kinase 1 controls components of a TORC2 signaling network in budding yeast.bioRxiv : the preprint server for biology · 2024Article
- The Ypk1 protein kinase signaling pathway is rewired and not essential for viability in Candida albicans.PLoS genetics · 2023Article
- Activation of CWI pathway through high hydrostatic pressure, enhancing glycerol efflux via the aquaglyceroporin Fps1 inMolecular biology of the cell · 2023Article
- Article
- Aft1 Nuclear Localization and Transcriptional Response to Iron Starvation Rely upon TORC2/Ypk1 Signaling and Sphingolipid Biosynthesis.International journal of molecular sciences · 2023Article
- Anti-Journal of fungi (Basel, Switzerland) · 2023Article
- The Rheb GTPase promotes pheromone blindness via a TORC1-independent pathway in the phytopathogenic fungus Ustilago maydis.PLoS genetics · 2022Article
- TOR complex 2 is a master regulator of plasma membrane homeostasis.The Biochemical journal · 2022Article
- Neomycin Interferes with Phosphatidylinositol-4,5-Bisphosphate at the Yeast Plasma Membrane and Activates the Cell Wall Integrity Pathway.International journal of molecular sciences · 2022Article
- Identification of Genes Promoting Growth ofJournal of fungi (Basel, Switzerland) · 2022Article
- Microdomain Protein Nce102 Is a Local Sensor of Plasma Membrane Sphingolipid Balance.Microbiology spectrum · 2022Article
- mTORC2 suppresses cell death induced by hypo-osmotic stress by promoting sphingomyelin transport.The Journal of cell biology · 2022Article
30 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The yeast AGC kinase orthologs Ypk1 and Ypk2 control several important cellular processes, including actin polarization, endocytosis, and sphingolipid metabolism. Activation of Ypk1/2 requires phosphorylation by kinases localized at the plasma membrane (PM), including the 3-phosphoinositide-dependent kinase 1 orthologs Pkh1/Pkh2 and the target of rapamycin complex 2 (TORC2). Unlike their mammalian counterparts SGK and Akt, Ypk1 and Ypk2 lack an identifiable lipid-targeting motif; therefore, how these proteins are recruited to the PM has remained elusive. To explore Ypk1/2 function, we constructed ATP analog-sensitive alleles of both kinases and monitored global changes in gene expression following their inhibition, where we observed increased expression of stress-responsive target genes controlled by Ca(2+)-dependent phosphatase calcineurin. TORC2 has been shown previously to negatively regulate calcineurin in part by phosphorylating two related proteins, Slm1 and Slm2, which associate with the PM via plextrin homology domains. We therefore investigated the relationship between Slm1 and Ypk1 and discovered that these proteins interact physically and that Slm1 recruits Ypk1 to the PM for phosphorylation by TORC2. We observed further that these steps facilitate subsequent phosphorylation of Ypk1 by Pkh1/2. Remarkably, a requirement for Slm1, can be bypassed by fusing the plextrin homology domain of Slm1 alone onto Ypk1, demonstrating that the essential function of Slm1 is largely attributable to its role in Ypk1 activation. These findings both extend the scope of cellular processes regulated by Ypk1/2 to include negative regulation of calcineurin and broaden the repertoire of mechanisms for membrane recruitment and activation of a protein kinase.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.