Characterization of hPRP4 kinase activation: potential role in signaling.
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.
Huang
Y
Y
Department of Medicine, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
Deng
T
T
Winston
B W
BW
D000818:Animals; D015152:Blotting, Northern; D019556:COS Cells; D005576:Colforsin / Q000378:metabolism; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000378:metabolism; D015723:Gene Library; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D017414:Ribonucleoprotein, U4-U6 Small Nuclear / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013912:Threonine / Q000378:metabolism; D014018:Tissue Distribution; D014157:Transcription Factors; D014162:Transfection; D050807:ets-Domain Protein Elk-1
D004268:DNA-Binding Proteins; C494112:ELK1 protein, human; D011518:Proto-Oncogene Proteins; D017414:Ribonucleoprotein, U4-U6 Small Nuclear; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D005576:Colforsin; D013912:Threonine; D004815:Epidermal Growth Factor; D008156:Luciferases; C489984:PRPF4B protein, human; D017346:Protein Serine-Threonine Kinases