Selective Activation of p38 Mitogen-activated Protein (MAP) Kinase Isoforms by the MAP Kinase Kinases MKK3 and MKK6

• Published in: The Journal of biological chemistry 1998-01, Vol.273 (3), p.1741-1748
• Main Authors: Enslen, Hervé, Raingeaud, Joël, Davis, Roger J.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Antibodies, Monoclonal; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Cloning, Molecular; Enzyme Activation; Enzyme Inhibitors - pharmacology; Humans; Imidazoles - pharmacology; Isoenzymes - metabolism; MAP Kinase Kinase 3; MAP Kinase Kinase 6; Mitogen-Activated Protein Kinase Kinases; Mitogen-Activated Protein Kinases; Molecular Sequence Data; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Protein-Serine-Threonine Kinases - metabolism; Protein-Tyrosine Kinases - metabolism; Pyridines - pharmacology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.3.1741

The cellular response to treatment with proinflammatory cytokines or exposure to environmental stress is mediated, in part, by the p38 group of mitogen-activated protein (MAP) kinases. We report the molecular cloning of a novel isoform of p38 MAP kinase, p38β2. This p38 MAP kinase, like p38α, is inhibited by the pyridinyl imidazole drug SB203580. The p38 MAP kinase kinase MKK6 is identified as a common activator of p38α, p38β2, and p38γ MAP kinase isoforms, while MKK3 activates only p38α and p38γ MAP kinase isoforms. The MKK3 and MKK6 signal transduction pathways are therefore coupled to distinct, but overlapping, groups of p38 MAP kinases.