MEKK1 phosphorylates MEK1 and MEK2 but does not cause activation of mitogen-activated protein kinase
| Autor: | Melanie H. Cobb, Jeffrey A. Frost, David J. Robbins, Carol A. Lange-Carter, Shuichan Xu, Alphonsus Dang |
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| Rok vydání: | 1995 |
| Předmět: |
MAP Kinase Kinase 2
Molecular Sequence Data MAP Kinase Kinase 1 MAP Kinase Kinase Kinase 1 Mitogen-activated protein kinase kinase Protein Serine-Threonine Kinases Transfection environment and public health MAP2K7 Substrate Specificity Mice Animals ASK1 c-Raf Phosphorylation MAPK14 Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase Kinases Multidisciplinary Binding Sites MAP kinase kinase kinase biology Base Sequence Chemistry Cyclin-dependent kinase 2 Protein-Tyrosine Kinases Peptide Fragments Recombinant Proteins Cell biology Rats Enzyme Activation Calcium-Calmodulin-Dependent Protein Kinases biology.protein Cyclin-dependent kinase 9 Signal Transduction Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 92(15) |
| ISSN: | 0027-8424 |
| Popis: | A constitutively active fragment of rat MEK kinase 1 (MEKK1) consisting of only its catalytic domain (MEKK-C) expressed in bacteria quantitatively activates recombinant mitogen-activated protein (MAP) kinase/extracellular signal-regulated protein kinase (ERK) kinases 1 and 2 (MEK1 and MEK2) in vitro. Activation of MEK1 by MEKK-C is accompanied by phosphorylation of S218 and S222, which are also phosphorylated by the protein kinases c-Mos and Raf-1. MEKK1 has been implicated in regulation of a parallel but distinct cascade that leads to phosphorylation of N-terminal sites on c-Jun; thus, its role in the MAP kinase pathway has been questioned. However, in addition to its capacity to phosphorylate MEK1 in vitro, MEKK-C interacts with MEK1 in the two-hybrid system, and expression of mouse MEKK1 or MEKK-C in mammalian cells causes constitutive activation of both MEK1 and MEK2. Neither cotransfected nor endogenous ERK2 is highly activated by MEKK1 compared to its stimulation by epidermal growth factor in spite of significant activation of endogenous MEK. Thus, other as yet undefined mechanisms may be involved in determining information flow through the MAP kinase and related pathways. |
| Databáze: | OpenAIRE |
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