The MKK7 gene encodes a group of c-Jun NH2-terminal kinase kinases
UMass Chan Affiliations
Department of Biochemistry and Molecular BiologyHoward Hughes Medical Institute and Program in Molecular Medicine
Document Type
ArticlePublication Date
1999-01-16Keywords
Alternative SplicingAmino Acid Sequence
Animals
COS Cells
Cell Line
Cell Nucleus
Chromosome Mapping
Cloning, Molecular
Cytoplasm
Enzyme ActivationHumansIn Situ Hybridization, FluorescenceIsoenzymes*MAP Kinase Kinase 4MAP Kinase Kinase 7MAP Kinase Kinase KinasesMice*Mitogen-Activated Protein Kinase KinasesMolecular Sequence DataProtein KinasesProtein-Serine-Threonine KinasesProtein-Tyrosine KinasesSequence Homology, Amino AcidLife SciencesMedicine and Health Sciences
Metadata
Show full item recordAbstract
The c-Jun NH2-terminal protein kinase (JNK) is a member of the mitogen-activated protein kinase (MAPK) group and is an essential component of a signaling cascade that is activated by exposure of cells to environmental stress. JNK activation is regulated by phosphorylation on both Thr and Tyr residues by a dual-specificity MAPK kinase (MAPKK). Two MAPKKs, MKK4 and MKK7, have been identified as JNK activators. Genetic studies demonstrate that MKK4 and MKK7 serve nonredundant functions as activators of JNK in vivo. We report here the molecular cloning of the gene that encodes MKK7 and demonstrate that six isoforms are created by alternative splicing to generate a group of protein kinases with three different NH2 termini (alpha, beta, and gamma isoforms) and two different COOH termini (1 and 2 isoforms). The MKK7alpha isoforms lack an NH2-terminal extension that is present in the other MKK7 isoforms. This NH2-terminal extension binds directly to the MKK7 substrate JNK. Comparison of the activities of the MKK7 isoforms demonstrates that the MKK7alpha isoforms exhibit lower activity, but a higher level of inducible fold activation, than the corresponding MKK7beta and MKK7gamma isoforms. Immunofluorescence analysis demonstrates that these MKK7 isoforms are detected in both cytoplasmic and nuclear compartments of cultured cells. The presence of MKK7 in the nucleus was not, however, required for JNK activation in vivo. These data establish that the MKK4 and MKK7 genes encode a group of protein kinases with different biochemical properties that mediate activation of JNK in response to extracellular stimuli.Source
Mol Cell Biol. 1999 Feb;19(2):1569-81.Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38579PubMed ID
9891090Related Resources
Link to Article in PubMedCollections
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