Volume 272, Number 38, Issue of September 19, 1997 pp. 23485-23488
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

COMMUNICATION:
Inhibition of Phosphatidylinositol 3-Kinase by c-Abl in the Genotoxic Stress Response

(Received for publication, June 19, 1997, and in revised form, July 21, 1997)

Zhi-Min Yuan , Taiju Utsugisawa , Yinyin Huang , Takatoshi Ishiko , Shuji Nakada , Surender Kharbanda , Ralph Weichselbaum and Donald Kufe

From the Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115 and the  Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois 60637

Activation of phosphatidylinositol (PI) 3-kinase by growth factors results in phosphorylation of phosphatidylinositol lipids at the D3 position. Although PI 3-kinase is essential to cell survival, little is known about mechanisms that negatively regulate this activity. Here we show that the c-Abl tyrosine kinase interacts directly with the p85 subunit of PI 3-kinase. Activation of c-Abl by ionizing radiation exposure is associated with c-Abl-dependent phosphorylation of PI 3-kinase. We also show that phosphorylation of p85 by c-Abl inhibits PI 3-kinase activity in vitro and in irradiated cells. These findings indicate that c-Abl negatively regulates PI 3-kinase in the stress response to DNA damage.

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