Inhibition of cap-dependent translation via phosphorylation of eIF4G by protein kinase Pak2.

ABSTRACT: Translation is downregulated in response to a variety of moderate stresses, including serum deprivation, hyperosmolarity and ionizing radiation. The cytostatic p21-activated protein kinase 2 (Pak2)/gamma-PAK is activated under the same stress conditions. Expression of wild-type Pak2 in cells and addition of Pak2 to reticulocyte lysate inhibit translation, while kinase-inactive mutants have no effect. Pak2 binds to and phosphorylates initiation factor (eIF)4G, which inhibits association of eIF4E with m(7)GTP, reducing initiation. The Pak2-binding site maps to the region on eIF4G that contains the eIF4E-binding site; Pak2 and eIF4E compete for binding to this site. Using an eIF4G-depleted reticulocyte lysate, reconstitution with mock-phosphorylated eIF4G fully restores translation, while pho

SUBMITTER: Ling J 

PROVIDER: S-EPMC1356308 | biostudies-literature | 2005 Dec

REPOSITORIES: biostudies-literature