Role of PIP2 and PIP3 binding proteins on cell growth signals

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1. Histons as novel PIP_2 binding proteinsWe found that PIP_2 bound to histon H_1 and H_3 and determined the binding sites. PIP_2 bound to the C-terminal 103 aminoacids. The amounts of PIP_2 bound to histon H_1 decreased when histon H_1 was phosphorylated by PKC.The addition of PIP_2 to histon H_1 suppressed the inhibitory effect of histon H_1 on basic transcriptional activity by RNA polymerase.2. PIP_2 phosphatase downstream of tyrosine kinaseWe purified 150kDa protein bound to Ash/Grb2 from bovine brain, and isolated its cDNA.P150 was found to have homology with synaptojanin. When P150 was expressed in Cos cells, actin stress fibers was disrupted and the cells showed multi-nuclear in shape. We purified P150 from bovine brain and characterized it. PIP_2 phosphatase activity was not inhibited by actin regulatory proteins such as cofilin, profilin and alpha-actinin, While PLCdelta_1 was inhibited. These results suggest that P150 hydrolyzes PIP_2 bound to actin regulatory proteins, resulting in reorganization of actin fibers.