| Structural highlights
Function
SLM1_YEAST Together with SLM2, effector of the TORC2- and calcineurin-signaling pathways. Phosphorylated and activated by TORC2 under favorable growth conditions. Mediates actin polarization via inhibition of calcineurin-dependent transcription. Upon nutrient limitation or environmental stress, gets dephosphorylated by calcineurin. Dephosphorylation inhibits its interaction with TORC2, thereby antagonizing TORC2 signaling and mediating calcineurin-dependent actin depolarization. Also functions in heat-induced, calcineurin-mediated uracil permease (FUR4) endocytosis.[1] [2] [3] [4]
Publication Abstract from PubMed
Protein-metabolite networks are central to biological systems, but are incompletely understood. Here, we report a screen to catalog protein-lipid interactions in yeast. We used arrays of 56 metabolites to measure lipid-binding fingerprints of 172 proteins, including 91 with predicted lipid-binding domains. We identified 530 protein-lipid associations, the majority of which are novel. To show the data set's biological value, we studied further several novel interactions with sphingolipids, a class of conserved bioactive lipids with an elusive mode of action. Integration of live-cell imaging suggests new cellular targets for these molecules, including several with pleckstrin homology (PH) domains. Validated interactions with Slm1, a regulator of actin polarization, show that PH domains can have unexpected lipid-binding specificities and can act as coincidence sensors for both phosphatidylinositol phosphates and phosphorylated sphingolipids.
A systematic screen for protein-lipid interactions in Saccharomyces cerevisiae.,Gallego O, Betts MJ, Gvozdenovic-Jeremic J, Maeda K, Matetzki C, Aguilar-Gurrieri C, Beltran-Alvarez P, Bonn S, Fernandez-Tornero C, Jensen LJ, Kuhn M, Trott J, Rybin V, Muller CW, Bork P, Kaksonen M, Russell RB, Gavin AC Mol Syst Biol. 2010 Nov 30;6:430. PMID:21119626[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Audhya A, Loewith R, Parsons AB, Gao L, Tabuchi M, Zhou H, Boone C, Hall MN, Emr SD. Genome-wide lethality screen identifies new PI4,5P2 effectors that regulate the actin cytoskeleton. EMBO J. 2004 Oct 1;23(19):3747-57. Epub 2004 Sep 16. PMID:15372071 doi:10.1038/sj.emboj.7600384
- ↑ Fadri M, Daquinag A, Wang S, Xue T, Kunz J. The pleckstrin homology domain proteins Slm1 and Slm2 are required for actin cytoskeleton organization in yeast and bind phosphatidylinositol-4,5-bisphosphate and TORC2. Mol Biol Cell. 2005 Apr;16(4):1883-900. Epub 2005 Feb 2. PMID:15689497 doi:E04-07-0564
- ↑ Mulet JM, Martin DE, Loewith R, Hall MN. Mutual antagonism of target of rapamycin and calcineurin signaling. J Biol Chem. 2006 Nov 3;281(44):33000-7. Epub 2006 Sep 7. PMID:16959779 doi:M604244200
- ↑ Bultynck G, Heath VL, Majeed AP, Galan JM, Haguenauer-Tsapis R, Cyert MS. Slm1 and slm2 are novel substrates of the calcineurin phosphatase required for heat stress-induced endocytosis of the yeast uracil permease. Mol Cell Biol. 2006 Jun;26(12):4729-45. PMID:16738335 doi:10.1128/MCB.01973-05
- ↑ Gallego O, Betts MJ, Gvozdenovic-Jeremic J, Maeda K, Matetzki C, Aguilar-Gurrieri C, Beltran-Alvarez P, Bonn S, Fernandez-Tornero C, Jensen LJ, Kuhn M, Trott J, Rybin V, Muller CW, Bork P, Kaksonen M, Russell RB, Gavin AC. A systematic screen for protein-lipid interactions in Saccharomyces cerevisiae. Mol Syst Biol. 2010 Nov 30;6:430. PMID:21119626 doi:10.1038/msb.2010.87
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