Tensin-2

Tyrosine-protein phosphatase which regulates cell motility, proliferation and muscle-response to insulin. Phosphatase activity is mediated by binding to phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3) via the SH2 domain. In muscles and under catabolic conditions, dephosphorylates IRS1 leading to its degradation and muscle atrophy. Negatively regulates PI3K-AKT pathway activation. Dephosphorylates nephrin NPHS1 in podocytes which regulates activity of the mTORC1 complex. 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. 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. Plays a role in promoting DLC1-dependent remodeling of the extracellular matrix.