| Structural highlights
Function
TENS2_HUMAN Tyrosine-protein phosphatase which regulates cell motility, proliferation and muscle-response to insulin (PubMed:15817639, PubMed:23401856). Phosphatase activity is mediated by binding to phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3) via the SH2 domain (PubMed:30092354). In muscles and under catabolic conditions, dephosphorylates IRS1 leading to its degradation and muscle atrophy (PubMed:23401856, PubMed:30092354). Negatively regulates PI3K-AKT pathway activation (PubMed:15817639, PubMed:23401856, PubMed:30092354). Dephosphorylates nephrin NPHS1 in podocytes which regulates activity of the mTORC1 complex (PubMed:28955049). Under normal glucose conditions, NPHS1 outcompetes IRS1 for binding to phosphatidylinositol 3-kinase (PI3K) which balances mTORC1 activity but high glucose conditions lead to up-regulation of TNS2, increased NPHS1 dephosphorylation and activation of mTORC1, contributing to podocyte hypertrophy and proteinuria (PubMed:28955049). Required for correct podocyte morphology, podocyte-glomerular basement membrane interaction and integrity of the glomerular filtration barrier (By similarity). Enhances RHOA activation in the presence of DLC1 (PubMed:26427649). Plays a role in promoting DLC1-dependent remodeling of the extracellular matrix (PubMed:20069572).[UniProtKB:Q8CGB6][1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
BACKGROUND: Src homology 2 (SH2) domain is a conserved module involved in various biological processes. Tensin family member was reported to be involved in tumor suppression by interacting with DLC-1 (deleted-in-liver-cancer-1) via its SH2 domain. We explore here the important questions that what the structure of tensin2 SH2 domain is, and how it binds to DLC-1, which might reveal a novel binding mode. PRINCIPAL FINDINGS: Tensin2 SH2 domain adopts a conserved SH2 fold that mainly consists of five beta-strands flanked by two alpha-helices. Most SH2 domains recognize phosphorylated ligands specifically. However, tensin2 SH2 domain was identified to interact with nonphosphorylated ligand (DLC-1) as well as phosphorylated ligand. CONCLUSIONS: We determined the solution structure of tensin2 SH2 domain using NMR spectroscopy, and revealed the interactions between tensin2 SH2 domain and its ligands in a phosphotyrosine-independent manner.
Solution structure of Tensin2 SH2 domain and its phosphotyrosine-independent interaction with DLC-1.,Dai K, Liao S, Zhang J, Zhang X, Tu X PLoS One. 2011;6(7):e21965. Epub 2011 Jul 12. PMID:21765928[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hafizi S, Ibraimi F, Dahlback B. C1-TEN is a negative regulator of the Akt/PKB signal transduction pathway and inhibits cell survival, proliferation, and migration. FASEB J. 2005 Jun;19(8):971-3. Epub 2005 Apr 7. PMID:15817639 doi:http://dx.doi.org/10.1096/fj.04-2532fje
- ↑ Clark K, Howe JD, Pullar CE, Green JA, Artym VV, Yamada KM, Critchley DR. Tensin 2 modulates cell contractility in 3D collagen gels through the RhoGAP DLC1. J Cell Biochem. 2010 Mar 1;109(4):808-17. PMID:20069572 doi:10.1002/jcb.22460
- ↑ Koh A, Lee MN, Yang YR, Jeong H, Ghim J, Noh J, Kim J, Ryu D, Park S, Song P, Koo SH, Leslie NR, Berggren PO, Choi JH, Suh PG, Ryu SH. C1-Ten is a protein tyrosine phosphatase of insulin receptor substrate 1 (IRS-1), regulating IRS-1 stability and muscle atrophy. Mol Cell Biol. 2013 Apr;33(8):1608-20. PMID:23401856 doi:10.1128/MCB.01447-12
- ↑ Shih YP, Sun P, Wang A, Lo SH. Tensin1 positively regulates RhoA activity through its interaction with DLC1. Biochim Biophys Acta. 2015 Dec;1853(12):3258-65. PMID:26427649 doi:10.1016/j.bbamcr.2015.09.028
- ↑ Lee J, Koh A, Jeong H, Kim E, Ha TS, Saleem MA, Ryu SH. C1-Ten is a PTPase of nephrin, regulating podocyte hypertrophy through mTORC1 activation. Sci Rep. 2017 Sep 27;7(1):12346. PMID:28955049 doi:10.1038/s41598-017-12382-8
- ↑ Kim E, Kim DH, Singaram I, Jeong H, Koh A, Lee J, Cho W, Ryu SH. Cellular phosphatase activity of C1-Ten/Tensin2 is controlled by Phosphatidylinositol-3,4,5-triphosphate binding through the C1-Ten/Tensin2 SH2 domain. Cell Signal. 2018 Nov;51:130-138. PMID:30092354 doi:10.1016/j.cellsig.2018.07.009
- ↑ Dai K, Liao S, Zhang J, Zhang X, Tu X. Solution structure of Tensin2 SH2 domain and its phosphotyrosine-independent interaction with DLC-1. PLoS One. 2011;6(7):e21965. Epub 2011 Jul 12. PMID:21765928 doi:10.1371/journal.pone.0021965
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