Summary

Name INPPL1
Full Name Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2
Synonyms Inositol polyphosphate phosphatase-like protein 1, INPPL-1, Protein 51C, SH2 domain-containing inositol 5'-phosphatase 2, SH2 domain-containing inositol phosphatase 2, SHIP-2 | SHIP2
Primary ID O15357
Links - -
Type protein
Relations 7
Function Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. Plays a central role in regulation of PI3K-dependent insulin signaling, although the precise molecular mechanisms and signaling pathways remain unclear. While overexpression reduces both insulin-stimulated MAP kinase and Akt activation, its absence does not affect insulin signaling or GLUT4 trafficking. Confers resistance to dietary obesity. May act by regulating AKT2, but not AKT1, phosphorylation at the plasma membrane. Part of a signaling pathway that regulates actin cytoskeleton remodeling. Required for the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation. Participates in regulation of cortical and submembraneous actin by hydrolyzing PtdIns(3,4,5)P3 thereby regulating membrane ruffling (PubMed:21624956). Regulates cell adhesion and cell spreading. Required for HGF-mediated lamellipodium formation, cell scattering and spreading. Acts as a negative regulator of EPHA2 receptor endocytosis by inhibiting via PI3K-dependent Rac1 activation. Acts as a regulator of neuritogenesis by regulating PtdIns(3,4,5)P3 level and is required to form an initial protrusive pattern, and later, maintain proper neurite outgrowth. Acts as a negative regulator of the FC-gamma-RIIA receptor (FCGR2A). Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Involved in EGF signaling pathway. Upon stimulation by EGF, it is recruited by EGFR and dephosphorylates PtdIns(3,4,5)P3. Plays a negative role in regulating the PI3K-PKB pathway, possibly by inhibiting PKB activity. Down-regulates Fc-gamma-R-mediated phagocytosis in macrophages independently of INPP5D/SHIP1. In macrophages, down-regulates NF-kappa-B-dependent gene transcription by regulating macrophage colony-stimulating factor (M-CSF)-induced signaling. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6. Involved in endochondral ossification.

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▶Modifications Tables

Relations

Regulator Mechanism target score ℹ
+ SRCup-regulates img/direct-activation.png phosphorylation INPPL1 0.551
Publications: 2 Organism: Homo Sapiens
+ INPPL1down-regulates img/direct_inhibition.png binding CBLC 0.2
Publications: 1 Organism: Homo Sapiens
+ INPPL1down-regulates img/indirect_inhibition.png AKT 0.635
Publications: 1 Organism: Homo Sapiens
+ INPPL1down-regulates img/indirect_inhibition.png AKT1 0.635
Publications: 1 Organism: Homo Sapiens
+ INPPL1down-regulates img/direct_inhibition.png chemical modification PIP3 0.8
Publications: 1 Organism: Homo Sapiens
+ INPPL1up-regulates img/indirect-activation.png MAPK8IP1 0.2
Publications: 1 Organism: Homo Sapiens