Characterization of hPRP4 Kinase Activation: Potential Role in Signaling

Autor: Huang, Yong, Deng, Tiliang, Winston, Brent W.
Zdroj: Biochemical and Biophysical Research Communications; May 10, 2000, Vol. 271 Issue: 2 p456-463, 8p
Abstrakt: Mitogen-activated protein kinases (MAPKs) and cyclin-dependent kinases (CDKs) are important proline-directed Ser/Thr kinases that play distinct roles in cell differentiation and proliferation. hPRP4 (pre-mRNA processing gene), a human homologue of S. pombe Prp4, is a recently isolated CDK-like kinase with homology to MAPKs. Little is known about the mRNA processing function of hPRP4 or about the signaling pathways with which it is associated. hPRP4 is expressed in a variety of human tissues with the highest expression in the brain, lung and liver. In this paper, we characterize the activation of hPRP4 in COS-7 cells and show that hPRP4 also possesses a transcription factor activation function. hPRP4 is activated by epidermal growth factor (EGF) or forskolin treatment, but not tetradecanoyl phorbol acetate (TPA) nor ultraviolet (UV) irradiation. Activated hPRP4 phosphorylates residue Thr-417 on Elk-1 resulting in Elk-1 activation. This site of Elk-1 phosphorylation is distinct from that of other MAPKs. Coexpression of hPRP4 with an Elk-1 reporter construct causes trans activation of the reporter. These findings suggest that hPRP4, a CDK-like kinase related to MAPKs, may play a distinct role in signal transduction in addition to its role in mRNA processing.
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