COT Kinase Proto-oncogene Expression in T Cells

Autor: Victor Calvo, Rosa de Gregorio, Estrella Sánchez-Góngora, Carlos Lisbona, Luis A. Pérez-Jurado, Alicia Ballester, Susana Alemany
Rok vydání: 2000
Předmět:
Zdroj: Journal of Biological Chemistry. 275:31379-31386
ISSN: 0021-9258
DOI: 10.1074/jbc.m000382200
Popis: COT/Tpl-2 proto-oncogene encodes a serine/threonine kinase implicated in cellular activation. In this study we have identified the human COT gene promoter region and three different human COT transcripts. These transcripts, with the same initiation site, display heterogeneity in their 5′ untranslated regions and in their subcellular localization. Activation of Jurkat T cells with either calcium ionophore A23187 or αCD3 and a phorbol ester increases the levels of the different COT transcripts. Analysis of the 5′ flanking region of the human COT gene reveals a unique transcription initiation site and a TATA element 20 nucleotides upstream. Transient expression of COT promoter constructs containing a reporter gene indicates that the transcriptional 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 ofCOT promoter, indicating that the inducible expression of the COT gene by T cell activating signals is mediated by the JNK/SAPK signal transduction pathway. All these data indicate stringent regulation of COT kinase proto-oncogene expression.
Databáze: OpenAIRE