PRAK, a novel protein kinase regulated by the p38 MAP kinase

Abstract

L.New and Y.Jiang contributed equally to this workWe have identified and cloned a novel serine/ threonine kinase, p38-regulated/activated protein kinase (PRAK). PRAK is a 471 amino acid protein with 20-30% sequence identity to the known MAP kinase-regulated protein kinases RSK1/2/3, MNK1/2 and MAPKAP-K2/3. PRAK was found to be expressed in all human tissues and cell lines examined. In HeLa cells, PRAK was activated in response to cellular stress and proinflammatory cytokines. PRAK activity was regulated by p38α and p38β both in vitro and in vivo and Thr182 was shown to be the regulatory phosphorylation site. Activated PRAK in turn phosphorylated small heat shock protein 27 (HSP27) at the physiologically relevant sites. An in-gel kinase assay demonstrated that PRAK is a major stress-activated kinase that can phosphorylate small heat shock protein, suggesting a potential role for PRAK in mediating stress-induced HSP27 phosphorylation in vivo.

Regulation of tyrosine hydroxylase by stress‐activated protein kinases

“…Here we have presented in vitro evidence for the participation of two novel stress-activated protein kinases, i.e. PRAK (New et al 1998) and MSK1 (Deak et al 1998) in the regulation of TH. These kinases are expressed in numerous human tissues, including heart, lung, placenta, liver, kidney, pancreas, muscle and brain, with the highest levels found in pancreas, muscle and brain (Deak et al 1998;New et al 1998).…”

“…PRAK (New et al 1998) and MSK1 (Deak et al 1998) in the regulation of TH. These kinases are expressed in numerous human tissues, including heart, lung, placenta, liver, kidney, pancreas, muscle and brain, with the highest levels found in pancreas, muscle and brain (Deak et al 1998;New et al 1998). Furthermore, using an MSK1 specific antibody, we have by western blotting confirmed that MSK1 is present in mouse adrenal glands and bovine adrenal medulla (unpublished data).…”

“…Several other downstream kinases of the SAPK2 pathway have been identified in recent years, including p38 regulated/ activated protein kinase (PRAK; New et al 1998;Ni et al 1998) and mitogen-and stress-activated protein kinase-1 (MSK1) and MSK2 (Deak et al 1998). Ser40 has been considered to be phosphorylated specifically by PKA in vivo (Vulliet et al 1985;Haycock and Haycock 1991;Lindgren et al 2000).…”

Activation and signaling of the p38 MAP kinase pathway

“…MNK1 is another kinase substrate of p38 whose function is thought to reside in translational initiation due to the observation that MNK1 and MNK2 can phosphorylate eukaryotic initiation factor-4e (eIF-4E) [59,60]. p38 regulated/activated kinase (PRAK) is a p38α and/or p38β activated kinase that shares 20-30% sequence identity to MK2 and is thought to regulate heat shock protein 27 (HSP27) [61]. Mitogen-and stress-activated protein kinase-1 (MSK1) can be directly activated by p38 and ERK, and may mediate activation of CREB [62][63][64].…”

Caenorhabditis elegans mom-4 is required for the activation of the p38 MAPK signaling pathway in the response to Pseudomonas aeruginosa infection

“…Our previous results have pointed out the complexity of the MAP kinase signaling pathway, which is due to the fact that each individual MAP kinase can be activated by two or three upstream MAP2Ks and multiple MAP3Ks in Drosophila under different stimuli (Zhuang et al, 2006). Upon activation, p38 can phosphorylate and activate a number of transcription factors including ATF-2/ATF-7, CHOP/GADD153, Elk1, MEF2-C, Sap1 and CREB (Wang et al,1996;Raingeaud et al,1996;Han et al,1997;Iordanov et al,1997;Whitmarsh et al,1997;Shivers et al, 2010), and protein kinases such as MAPKAPK2, MNK, PRAK, MSK1 and RSK-B (Stokoe et al,1992;Fukunaga et al,1997;Waskiewicz et al,1997;New et al,1998;Deak et al,1998;Pierrat et al,1998), thus eliciting different cellular responses.…”