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

• Published in: The Journal of biological chemistry Vol. 275; no. 40; pp. 31379 - 31386
• Main Authors: Sánchez-Góngora, E, Lisbona, C, de Gregorio, R, Ballester, A, Calvo, V, Pérez-Jurado, L, Alemany, S
• Format: Journal Article
• Language: English
• Published: United States 06.10.2000
• Subjects: 5' Untranslated Regions; Base Sequence; Blotting, Northern; Calcimycin - pharmacology; calcium ionophores; CD3 Complex - metabolism; Cell Cycle; COT gene; Genes, Dominant; Humans; Immunoblotting; Ionophores - pharmacology; JNK protein; Jurkat Cells; Luciferases - metabolism; MAP Kinase Kinase Kinases - genetics; Mitogen-Activated Protein Kinase 8; Mitogen-Activated Protein Kinases - metabolism; Molecular Sequence Data; Phorbol Esters - metabolism; Promoter Regions, Genetic; Proto-Oncogene Proteins - genetics; Reverse Transcriptase Polymerase Chain Reaction; Ribonucleases - metabolism; RNA, Messenger - metabolism; SAPK protein; Signal Transduction; Single-Strand Specific DNA and RNA Endonucleases - metabolism; T-Lymphocytes - metabolism; Tpl-2 gene; Transcription, Genetic; Transfection; Up-Regulation
• ISSN: 0021-9258
• DOI: 10.1074/jbc.M000382200

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 or alphaCD3 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 of COT 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.