3voq
From Proteopedia
Revision as of 20:33, 25 December 2014
Crystal structure of the pleckstrin homology domain of human Sin1, a TORC2 subunit
Structural highlights
Function[SIN1_HUMAN] Subunit of mTORC2, which regulates cell growth and survival in response to hormonal signals. mTORC2 is activated by growth factors, but, in contrast to mTORC1, seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'. Within mTORC2, MAPKAP1 is required for complex formation and mTORC2 kinase activity. MAPKAP1 inhibits MAP3K2 by preventing its dimerization and autophosphorylation. Inhibits HRAS and KRAS signaling. Enhances osmotic stress-induced phosphorylation of ATF2 and ATF2-mediated transcription.[1] [2] [3] [4] [5] Publication Abstract from PubMedIn eukaryotes, multiprotein complexes termed TOR complex 1 (TORC1) and TOR complex 2 (TORC2) function as major regulators of cell growth, metabolism and ageing. The C-terminal domain of the Saccharomyces cerevisiae TORC2 component Avo1 is required for plasma-membrane localization of TORC2 and is essential for yeast viability. X-ray crystal structures of the C-terminal domain of Avo1 and of its human orthologue Sin1 have been determined. The structures show that the C-termini of Avo1 and Sin1 both have the pleckstrin homology (PH) domain fold. Comparison with known PH-domain structures suggests a putative binding site for phosphoinositides. Structures of the pleckstrin homology domain of Saccharomyces cerevisiae Avo1 and its human orthologue Sin1, an essential subunit of TOR complex 2.,Pan D, Matsuura Y Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Apr 1;68(Pt 4):386-92., Epub 2012 Mar 27. PMID:22505404[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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