ZPK inhibits PKA induced transcriptional activation by CREB and blocks retinoic acid induced neuronal differentiation.
Zipper Protein Kinase (ZPK) is a leucine zipper protein localized to the nucleus which exhibits serine-threonine kinase activity and is associated with the stress dependent signal transduction pathway. ZPK forms heterodimers with leucine zipper containing transcription factors such as the cyclic AMP responsive element binding protein (CREB) and Myc. Furthermore ZPK phosphorylates both Myc and CREB. Overexpression of ZPK in NTera-2 human teratocarcinoma cells results in inhibition of PKA induced transcriptional activation by CREB and prevents retinoic acid induced differentiation of the cells to neurons. Our results suggest that ZPK stifles neural differentiation of NT-2 cells partly due to its inhibitory effect on CREB function.
Reddy
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Department of Neurology Research, Children's Hospital of Philadelphia, University of Pennsylvania, 19104, USA.
Basu
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Bannerman
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Ikegaki
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Reddy
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Pleasure
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D016475:3T3 Cells; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D003001:Cloning, Molecular; D017362:Cyclic AMP Response Element-Binding Protein / Q000302:isolation & purification / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D020930:MAP Kinase Kinase Kinases; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D018243:Teratocarcinoma; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D017362:Cyclic AMP Response Element-Binding Protein; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D014212:Tretinoin; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D020930:MAP Kinase Kinase Kinases; C090757:mitogen-activated protein kinase kinase kinase 12