Mouse Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificit

In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement (By similarity).

Tumor suppressor.

Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.

Also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5-tetrakisphosphate with order of substrate preference in vitro PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4.

The lipid phosphatase activity is critical for its tumor suppressor function.

Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival.

The unphosphorylated form cooperates with MAGI2 to suppress AKT1 activation.

Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation.

Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation.

May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue.

The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability.

{ECO:0000250, ECO:0000269|PubMed:10339565, ECO:0000269|PubMed:19778506}.