The BioGRID | PUBLICATION VIEW

	J. Biol. Chem. Aug (1995); 270(32):18871-4
Ionizing radiation stimulates a Grb2-mediated association of the stress-activated protein kinase with phosphatidylinositol 3-kinase.
Kharbanda S, Saleem A, Shafman T, Emoto Y, Taneja N, Rubin E, Weichselbaum R, Woodgett J, Avruch J, Kyriakis J
Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Abstract: The stress-activated protein (SAP) kinases are induced by tumor necrosis factor, oncoproteins, and UV light. The present studies demonstrate that ionizing radiation (IR) activates p54 SAP kinase. IR-induced activation of SAP kinase is associated with binding to the SH2/SH3-containing adaptor protein Grb2. This interaction is mediated by the SH3 domains of Grb2 and the proline-rich sequence PPPKIP in the carboxy-terminal region of SAP kinase. We also demonstrated that SAP kinase and the p85 alpha-subunit of phosphatidylinositol (PI) 3-kinase form a complex in irradiated cells. The results indicate that this complex involves binding of the p85 alpha subunit of PI 3-kinase to the SH2 domain of Grb2. The functional role of linking SAP kinase to PI 3-kinase is further supported by the finding that wortmannin, an inhibitor of PI 3-kinase, stimulates SAP kinase activity. These results suggest that the cellular response to IR may include regulation of SAP kinase by a PI 3-kinase-dependent signaling pathway.
[PUBMED: 7642542]