Ionizing Radiation Stimulates a Grb2-mediated Association of the Stress-activated Protein Kinase with Phosphatidylinositol 3-Kinase (*)

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 carboxyl-terminal region of SAP kinase. We also demonstrate that SAP kinase and the p85α-subunit of phosphatidylinositol (PI) 3-kinase form a complex in irradiated cells. The results indicate that this complex involves binding of the p85α 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.

• Publication year

  1995

• Venue

  Journal of Biological Chemistry

• Publication date

  1995-08-11

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.270.32.18871PMID 7642542
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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