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.
Publication types
-
Research Support, Non-U.S. Gov't
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
Substances
-
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)