A Family of Stress-Inducible GADD45-like Proteins Mediate Activation of the Stress-Responsive MTK1/MEKK4 MAPKKK
Copyright policy )A Family of Stress-Inducible GADD45-like Proteins Mediate Activation of the Stress-Responsive MTK1/MEKK4 MAPKKK
The stress-responsive p38 and JNK MAPK pathways regulate cell cycle and apoptosis. A human MAPKKK, MTK1 (= MEKK4), mediates activation of both p38 and JNK in response to environmental stresses. Using a yeast two-hybrid method, three related proteins, GADD45alpha (= GADD45), GADD45, (= MyD118), and GADD45gamma, were identified that bound to an N-terminal domain of MTK1. These proteins activated MTK1 kinase activity, both in vivo and in vitro. The GADD45-like genes are induced by environmental stresses, including MMS, UV, and gamma irradiation. Expression of the GADD45-like genes induces p38/JNK activation and apoptosis, which can be partially suppressed by coexpression of a dominant inhibitory MTK1 mutant protein. We propose that the GADD45-like proteins mediate activation of the p38/JNK pathway, via MTK1/ MEKK4, in response to environmental stresses.
- Dana-Farber Cancer Institute United States
- Harvard University United States
Biochemistry, Genetics and Molecular Biology(all), Molecular Sequence Data, Intracellular Signaling Peptides and Proteins, Apoptosis, MAP Kinase Kinase Kinases, MAP Kinase Kinase Kinase 4, Peptide Mapping, Enzyme Activation, Gene Expression Regulation, Multigene Family, Protein Biosynthesis, COS Cells, Calcium-Calmodulin-Dependent Protein Kinases, Animals, Humans, Amino Acid Sequence, Mitogen-Activated Protein Kinases, Cells, Cultured, DNA Damage, HeLa Cells, Protein Binding
Biochemistry, Genetics and Molecular Biology(all), Molecular Sequence Data, Intracellular Signaling Peptides and Proteins, Apoptosis, MAP Kinase Kinase Kinases, MAP Kinase Kinase Kinase 4, Peptide Mapping, Enzyme Activation, Gene Expression Regulation, Multigene Family, Protein Biosynthesis, COS Cells, Calcium-Calmodulin-Dependent Protein Kinases, Animals, Humans, Amino Acid Sequence, Mitogen-Activated Protein Kinases, Cells, Cultured, DNA Damage, HeLa Cells, Protein Binding
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