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 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.
Sánchez-Góngora
E
E
Instituto de Investigaciones Biomedicas, Consejo Superior de Investigaciones Cientificas, Facultad Medicina Universidad Autonoma de Madrid, Arturo Duperier 4, 28029 Madrid, Spain.
Lisbona
C
C
de Gregorio
R
R
Ballester
A
A
Calvo
V
V
Pérez-Jurado
L
L
Alemany
S
S
D020121:5' Untranslated Regions; D001483:Base Sequence; D015152:Blotting, Northern; D017252:CD3 Complex / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002453:Cell Cycle; D005799:Genes, Dominant; D006801:Humans; D015151:Immunoblotting; D007476:Ionophores / Q000494:pharmacology; D019169:Jurkat Cells; D008156:Luciferases / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000235:genetics*; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D010703:Phorbol Esters / Q000378:metabolism; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012260:Ribonucleases / Q000378:metabolism; D015398:Signal Transduction; D015719:Single-Strand Specific DNA and RNA Endonucleases / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation
D020121:5' Untranslated Regions; D017252:CD3 Complex; D007476:Ionophores; C000715470:MAS1 protein, human; D010703:Phorbol Esters; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D000001:Calcimycin; D008156:Luciferases; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; C069937:MAP3K8 protein, human; D012260:Ribonucleases; D015719:Single-Strand Specific DNA and RNA Endonucleases