SH2-mediated steric occlusion of the C2 domain regulates autoinhibition of SHIP1 inositol 5-phosphatase.

ABSTRACT: The Src homology 2 (SH2) domain-containing inositol polyphosphate 5-phosphatase 1 (SHIP1) is an immune cell-specific enzyme that regulates phosphatidylinositol-(3,4,5)-trisphosphate signaling at the plasma membrane following receptor activation. SHIP1 plays an important role in processes, such as directed cell migration, endocytosis, and cortical membrane oscillations. Alterations in SHIP1 expression have been shown to perturb myeloid cell chemotaxis and differentiation. In the brain, SHIP1 regulates microglial cell behaviors, which have been linked to Alzheimer's disease. Understanding the structural and functional relationships of SHIP1 is critical for developing ways to modulate SHIP1 membrane localization and lipid phosphatase activity during immune cell signaling. Recently, we discove

SUBMITTER: Drew EE 

PROVIDER: S-EPMC12657763 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature