3voq | pdb_00003voq
Crystal structure of the pleckstrin homology domain of human Sin1, a TORC2 subunit
Template:ABSTRACT PUBMED 22505404
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]
About this Structure
3voq is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Pan D, Matsuura Y. Structures of the pleckstrin homology domain of Saccharomyces cerevisiae Avo1 and its human orthologue Sin1, an essential subunit of TOR complex 2. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Apr 1;68(Pt 4):386-92., Epub 2012 Mar 27. PMID:22505404 doi:10.1107/S1744309112007178
- ↑ Cheng J, Zhang D, Kim K, Zhao Y, Zhao Y, Su B. Mip1, an MEKK2-interacting protein, controls MEKK2 dimerization and activation. Mol Cell Biol. 2005 Jul;25(14):5955-64. PMID:15988011 doi:25/14/5955
- ↑ Jacinto E, Facchinetti V, Liu D, Soto N, Wei S, Jung SY, Huang Q, Qin J, Su B. SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity. Cell. 2006 Oct 6;127(1):125-37. Epub 2006 Sep 7. PMID:16962653 doi:S0092-8674(06)01147-0
- ↑ Makino C, Sano Y, Shinagawa T, Millar JB, Ishii S. Sin1 binds to both ATF-2 and p38 and enhances ATF-2-dependent transcription in an SAPK signaling pathway. Genes Cells. 2006 Nov;11(11):1239-51. PMID:17054722 doi:GTC1016
- ↑ Yang Q, Inoki K, Ikenoue T, Guan KL. Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity. Genes Dev. 2006 Oct 15;20(20):2820-32. PMID:17043309 doi:10.1101/gad.1461206
- ↑ Schroder WA, Buck M, Cloonan N, Hancock JF, Suhrbier A, Sculley T, Bushell G. Human Sin1 contains Ras-binding and pleckstrin homology domains and suppresses Ras signalling. Cell Signal. 2007 Jun;19(6):1279-89. Epub 2007 Jan 20. PMID:17303383 doi:10.1016/j.cellsig.2007.01.013
