Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel MAP kinase kinase kinase.
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, Cells, Cultured, Cercopithecus aethiops, DNA Primers, Enzyme Activation, Fetal Proteins, 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, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-raf, Proto-Oncogene Proteins p21(ras), Receptor Protein-Tyrosine Kinases, Receptor, EphA4, Signal Transduction, T-Lymphocytes
Animals, Base Sequence, Calcium-Calmodulin-Dependent Protein Kinases, Cells, Cultured, Cercopithecus aethiops, DNA Primers, Enzyme Activation, Fetal Proteins, 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, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-raf, Proto-Oncogene Proteins p21(ras), Receptor Protein-Tyrosine Kinases, Receptor, EphA4, Signal Transduction, T-Lymphocytes
EMBO J.
Date: Feb. 15, 1996
PubMed ID: 8631303
View in: Pubmed Google Scholar
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