Overexpression of phosphatidylinositol phosphate 5-kinase alpha (PIP5KIalpha), which synthesizes PIP2, suppresses apoptosis, whereas a kinase-deficient mutant does not. Protection by the wild-type PIP5KIalpha isaccompanied by decreases in the generation of activated caspases and of caspase 3-cleaved PARP. Protection is not mediated through PIP3 or Akt activation. An anti-apoptotic role for PIP(2) is substantiated by the finding that PIP5KIalpha is cleaved by caspase 3 during apoptosis, and cleavage inactivates PIP5KIalpha in vitro. Mutation of the P(4) position (D279A) of the PIP5KIalpha caspase 3 cleavage consensus prevents cleavage in vitro, and during apoptosis in vivo. Significantly, the caspase 3-resistant PIP5KIalpha mutant is more effective in suppressing apoptosis than the wild-type kinase. PIP2 is a direct regulator of apical and effector caspases in the death receptor and mitochondrial pathways, and PIP5KIalpha inactivation contributes to the progression of apoptosis.
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Protein Aliases: 68 kDa type I phosphatidylinositol 4-phosphate 5-kinase; 68 kDa type I phosphatidylinositol 4-phosphate 5-kinase alpha; 68 kDa type I phosphatidylinositol-4-phosphate 5-kinase; 68 kDa type I phosphatidylinositol-4-phosphate 5-kinase alpha; Phosphatidylinositol 4-phosphate 5-kinase type I alpha; Phosphatidylinositol 4-phosphate 5-kinase type I beta; Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha; phosphatidylinositol-4-phosphate 5-kinase; phosphatidylinositol-4-phosphate 5-kinase type I alpha; phosphatidylinositol-4-phosphate 5-kinase type-1 alpha; phosphatidylinositol-4-phosphate 5-kinase, type 1 beta; phosphatidylinositol-4-phosphate 5-kinase, type I, alpha; PI4P5KIbeta; PI51A; PIP5K1-alpha; PIP5KIalpha; ptdIns(4)P-5-kinase 1 alpha
Gene Aliases: PI4P5K-I[a]; PIP5K1-alpha; PIP5K1A; Pip5k1b; PIP5KIalpha; Pipk5a