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 .
Subcellular locations: Cell junction, Focal adhesion, Cell membrane, Cytoplasm
Detected at the end of actin stress fibers. Detected in cytoplasmic punctate bodies (, ). Localizes to both focal adhesions and fibrillar adhesions but is found mainly in focal adhesions . Enriched in dynamic focal adhesions at the leading edge of the cell and is found only rarely in fibrillar adhesions on the ventral surface of cells .
Detected in heart, kidney, brain, thymus, spleen, liver, placenta, lung, skeletal muscle and small intestine.