An essential role for the SHIP2-dependent negative feedback loop in neuritogenesis of nerve growth factor-stimulated PC12 cells.

ABSTRACT: The local accumulation of phosphatidylinositol (3,4,5) trisphosphate (PIP(3)) and resulting activation of Rac1/Cdc42 play a critical role in nerve growth factor (NGF)-induced neurite outgrowth. To further explore the mechanism, we visualized PIP(3), phosphatidylinositol (3,4) bisphosphate, and Rac1/Cdc42 activities by fluorescence resonance energy transfer (FRET) imaging in NGF-stimulated PC12 cells. Based on the obtained FRET images, and with the help of in silico kinetic reaction model, we predicted that PI-5-phosphatase negatively regulates PIP(3) upon NGF stimulation. In agreement with this model, depletion of Src homology 2 domain-containing inositol polyphosphate 5-phosphatase 2 (SHIP2) markedly potentiated NGF-induced Rac1/Cdc42 activation and PIP(3) accumulation and considerably in

SUBMITTER: Aoki K 

PROVIDER: S-EPMC2064282 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature