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PMID: 8631303 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 15 ·No. 4 ·1996-02-15 ·Pages 817-26

Salmeron A, Ahmad TB, Carlile GW, Pappin D, Narsimhan RP, Ley SC

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.

MeSH Terms
Animals Base Sequence Calcium-Calmodulin-Dependent Protein Kinases/metabolism Cells, Cultured Chlorocebus 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
Chemicals
DNA Primers Fetal Proteins Proto-Oncogene Proteins Protein Kinases Protein-Tyrosine Kinases Receptor Protein-Tyrosine Kinases Receptor, EphA4 Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-raf Calcium-Calmodulin-Dependent Protein Kinases Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases MAP Kinase Kinase Kinases MAP3K8 protein, human MAP Kinase Kinase 1 MAP Kinase Kinase 4 MAP2K1 protein, human MAP2K4 protein, human Mitogen-Activated Protein Kinase Kinases HRAS protein, human Proto-Oncogene Proteins p21(ras)
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Salmeron A
Division of Cellular Immunology, National Institute of Medical Research, London, UK.
Ahmad T B
Carlile G W
Pappin D
Narsimhan R P
Ley S C
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1996-02-15
Pages
817-26
Language
English
Region
England
NLM ID
8208664
PMCID
PMC450280
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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