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J Biol Chem, Vol. 274, Issue 51, 36790-36795, December 17, 1999

Novel Inositol Polyphosphate 5-Phosphatase Localizes at Membrane Ruffles^*

Yasuhiro Mochizuki and Tadaomi Takenawa

From the Department of Biochemistry, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan

We have cloned a novel inositol polyphosphate 5-phosphatase from the rat brain cDNA library. It contains two highly conserved 5-phosphatase motifs, both of which are essential for its enzymatic activity. Interestingly, the proline content of this protein is high and concentrated in its N- and C-terminal regions. One putative SH3-binding motif and six 14-3-3 -binding motifs were found in the amino acid sequence. This enzyme hydrolyzed phosphate at the D-5 position of inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, and phosphatidylinositol 4,5-bisphosphate, consistent with the substrate specificity of type II 5-phosphatase, OCRL, synaptojanin and synaptojanin 2, already characterized 5-phosphatases. When the Myc-epitope-tagged enzyme was expressed in COS-7 cells and stained with anti-Myc polyclonal antibody, a signal was observed at ruffling membranes and in the cytoplasm. We prepared several deletion mutants and demonstrated that the 123 N-terminal amino acids (311-433) and a C-terminal proline-rich region containing 277 amino acids (725-1001) were essential for its localization to ruffling membranes. This enzyme might regulate the level of inositol and phosphatidylinositol polyphosphates at membrane ruffles.

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^* This work was supported in part by a grant-in-aid for Research for the Future Program from the Japan Society for the Promotion of Science.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Tel.: 81-3-5449-5508; Fax: 81-3-5449-5417; E-mail: takenawa@ims.u-tokyo.ac.jp.

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Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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