Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel MAP kinase kinase kinase

Salmeron, A., Ahmad, T. B., Carlile, G. W., Pappin, D., Narsimhan, R. P., Ley, S. C. (February 1996) Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel MAP kinase kinase kinase. Embo Journal, 15 (4). pp. 817-26. ISSN 0261-4189

URL: http://www.ncbi.nlm.nih.gov/pubmed/8631303

Abstract

The Tpl-2 protein serine/threonine kinase was originally identified, in a C-terminally deleted form, as the product of an oncogene associated with the progression of Moloney murine leukemia virus-induced T cell lymphomas in rats. The kinase domain of Tpl-2 is homologous to the Saccharomyces cerevisiae gene product, STE11, which encodes a MAP kinase kinase kinase. This suggested that Tpl-2 might have a similar activity. Consistent with this hypothesis, immunoprecipitated Tpl-2 and Tpl-2deltaC (a C-terminally truncated mutant) phosphorylated and activated recombinant fusion proteins of the mammalian MAP kinase kinases, MEK-1 and SEK-1, in vitro. Furthermore, transfection of Tpl-2 into COS-1 cells or Jurkat T cells. markedly activated the MAP kinases, ERK-1 and SAP kinase (JNK), which are substrates for MEK-1 and SEK-1, respectively. Tpl-2, therefore, is a MAP kinase kinase kinase which can activate two MAP kinase pathways. After Raf and Mos, Tpl-2 is the third serine/threonine oncoprotein kinase that has been shown to function as a direct activator of MEK-1.

Item Type: Paper
Additional Information: Salmeron, A Ahmad, T B Carlile, G W Pappin, D Narsimhan, R P Ley, S C Research Support, Non-U.S. Gov't England The EMBO journal EMBO J. 1996 Feb 15;15(4):817-26.
Uncontrolled Keywords: Animals Base Sequence Calcium-Calmodulin-Dependent Protein Kinases/metabolism Cells, Cultured Cercopithecus aethiops DNA Primers/chemistry Enzyme Activation Fetal Proteins/ metabolism Humans MAP Kinase Kinase 1 MAP Kinase Kinase 4 MAP Kinase Kinase Kinases Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinase Kinases Mitogen-Activated Protein Kinases Molecular Sequence Data Phosphorylation Protein Kinases/ metabolism Protein-Serine-Threonine Kinases/ metabolism Protein-Tyrosine Kinases/ metabolism Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-raf Proto-Oncogene Proteins p21(ras)/metabolism Receptor Protein-Tyrosine Kinases/ metabolism Receptor, EphA4 Signal Transduction T-Lymphocytes
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > Mitogen-activated protein kinase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression > phosphorylation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein receptor
organs, tissues, organelles, cell types and functions > tissues types and functions > signal transduction
CSHL Authors:
Communities: CSHL labs > Pappin lab
Depositing User: Kathleen Darby
Date: 15 February 1996
Date Deposited: 13 May 2014 15:46
Last Modified: 13 May 2014 15:46
PMCID: 450280
Related URLs:
URI: https://repository.cshl.edu/id/eprint/30104

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving