Sprouty2 regulates PI(4,5)P2/Ca2+ signaling and HIV-1 Gag release.

摘要: We reported recently that activation of the inositol 1,4,5-triphosphate receptor (IP3R) is required for efficient HIV-1 Gag trafficking and viral particle release. IP3R requires phospholipase C (PLC)-catalyzed hydrolysis PI(4,5)P(2) to IP3 diacylglycerol. show Sprouty2 (Spry2), which binds PLCγ, interfered with in a manner similar U73122, an inhibitor hydrolysis, suggesting Spry2 negatively regulates by preventing formation its activating ligand, IP3. Mutation Asp R252, crucial determinant binding C-terminal domain Spry2, prevented interference, indicating phospholipid required. By contrast, deletion PLCγ region or mutation critical Tyr residue did not prevent interference but Spry2-PI(4,5)P(2) colocalization was detected, PLC their stable association. Like over-expression inhibited wild type release as virus-like particles. Disrupting either relieved inhibition. IP3R-mediated Ca(2+)signaling, turn, found influence subcellular distribution ERK, regulator. Our findings suggest influences function through control controlling ERK activation.