PRAK, A NOVEL PROTEIN-KINASE REGULATED BY THE P38 MAP KINASE

We have identified and cloned a novel serine/threonine kinase, p38-reg ulated/activated protein kinase (PRAK). PRAK is a 471 amino acid prote in with 20-30% sequence identity to the known MAP kinase-regulated pro tein kinases RSK1/2/3, MNK1/2 and MAPKAP-K2/3. PRAK was found to be ex pressed in all human tissues and cell lines examined. In HeLa cells, P RAK was activated in response to cellular stress and proinflammatory c ytokines. PRAK activity was regulated by p38 alpha and p38 beta both i n vitro and in vivo and Thr182 was shown to be the regulatory phosphor ylation site. Activated PRAK in turn phosphorylated small heat shock p rotein 27 (HSP27) at the physiologically relevant sites. An in-gel kin ase assay demonstrated that PRAK is a major stress-activated kinase th at can phosphorylate small heat shock protein, suggesting a potential role for PRAK in mediating stress-induced HSP27 phosphorylation in viv o.