COT kinase proto-oncogene expression in T cells - Implication of the JNK/SAPK signal transduction pathway in COT promoter activation

COT/Tpl-2 proto oncogene encodes a serine/threonine kinase implicated in ce llular activation. In this study we have identified the human COT gene prom oter region and three different human COT transcripts. These transcripts, w ith the same initiation site, display heterogeneity in their 5' untranslate d regions and in their subcellular localization. Activation of Jurkat T cel ls with either calcium ionophore A23187 or alpha CD3 and a phorbol ester in creases the levels of the different COT transcripts. Analysis of the 5' fla nking region of the human COT gene reveals a unique transcription initiatio n site and a TATA element 20 nucleotides upstream. Transient expression of COT promoter constructs containing a reporter gene indicates that the trans criptional activity of the 5' flanking region of the COT gene is regulated by T cell-activating signals. Cotransfection of a dominant negative version of SEK-2 abolishes the inducible transcriptional activity of COT promoter, indicating that the inducible expression of the COT gene by T cell activat ing signals is mediated by the JNK/SAPK signal transduction pathway. All th ese data indicate stringent regulation of COT kinase proto-oncogene express ion.