PI(3,4,5)P3 regulates the interaction between Akt and B23 in the nucleus

• Published in: BMB reports Vol. 43; no. 2; pp. 127 - 132
• Main Authors: Kwon, I.S., Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea, Lee, K.H., Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea, Choi, J.W., Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea, Ahn, J.Y., Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
• Format: Journal Article
• Language: English
• Published: Korea (South) 생화학분자생물학회 01.02.2010
• Subjects: Akt; Animals; B23; Cell Line, Tumor; Cell Nucleus - metabolism; Neuronal cell; NOYAU CELLULAIRE; Nuclear PIP3; Nuclear Proteins - metabolism; NUCLEO; NUCLEUS; Phosphatidylinositols - metabolism; Protein Structure, Tertiary; Proto-Oncogene Proteins c-akt - metabolism; Rats; Subcellular dynamics; 화학
• ISSN: 1976-6696; 1976-670X
• DOI: 10.5483/bmbrep.2010.43.2.127

Phosphatidylinositol (3,4,5)-triphosphate (PIP₃) is a lipid second messenger that employs a wide range of downstream effector proteins for the regulation of cellular processes, including cell survival, polarization and proliferation. One of the most well characterized cytoplasmic targets of PIP₃, serine/threonine protein kinase B (PKB)/Akt, promotes cell survival by directly interacting with nucleophosmin (NPM)/B23, the nuclear target of PIP₃. Here, we report that nuclear PIP₃ competes with Akt to preferentially bind B23 in the nucleoplasm. Mutation of Arg23 and Arg25 in the PH domain of Akt prevents binding to PIP₃, but does not disrupt the Akt/B23 interaction. However, treatment with phosphatases PTEN or SHIP abrogates the association between Akt and B23, indicating that nuclear PIP₃ regulates the Akt/B23 interaction by controlling the concentration and subcellular dynamics of these two proteins.