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J Biol Chem, Vol. 274, Issue 7, 3919-3922, February 12, 1999

COMMUNICATION
Evidence That a Phosphatidylinositol 3,4,5-Trisphosphate-binding Protein Can Function in Nucleus

Kenichi Tanaka, Kaori Horiguchi, Toshinori Yoshida^¶, Makio Takeda^¶, Hideki Fujisawa^¶, Kenichi Takeuchi, Masato Umeda, Sigeaki Kato^**, Sayoko Ihara, Satoshi Nagata, and Yasuhisa Fukui

From the  Laboratory of Biological Chemistry, Department of Applied Biological Chemistry, Graduate School of Agriculture and Life Science, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, the ^¶ Toxicology Division, Institute of Environmental Toxicology, 4321 Uchimoriya-cho, Mitsukaido-shi, Ibaraki 303-0043, the  Department of Inflammation Research, The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8613, and the ^** Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan

PIP₃BP is a phosphatidylinositol 3,4,5-trisphosphate-binding protein (PIP₃BP) abundant in brain, containing a zinc finger motif and two pleckstrin homology (PH) domains. Staining of rat brain cells with anti-PIP₃BP antibody and determination of localization of PIP₃BP fused to the green fluorescent protein (GFP-PIP₃BP) revealed that PIP₃BP was targeted to the nucleus. Targeting was dependent on a putative nuclear localization signal in PIP₃BP. Generation of PIP₃ in the nucleus was detected in H₂O₂-treated 293T cells, nerve growth factor (NGF)-treated PC12 cells, and platelet-derived growth factor (PDGF)-treated NIH 3T3 cells. Translocation of phosphatidylinositol 3-kinase (PI 3-kinase) to the nucleus and enhanced activity of PI 3-kinase in the nucleus fraction were observed after H₂O₂ treatment of 293T cells, suggesting that PI 3-kinase can be activated in the nucleus as well as in the membrane after appropriate stimulation of the cells. Co-expression of the constitutively active PI 3-kinase with PIP₃BP resulted in exportation of the protein from the nucleus to the cytoplasm, suggesting that PIP₃BP can function as a PIP₃-binding protein in the intact cells. These results imply that there may be an unknown function of PI 3-kinase in the nucleus.

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

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