Selective interaction of JNK protein kinase isoforms with transcription factors
Whitmarsh, Alan J.
Sluss, Hayla Karen
Davis, Roger J.
UMass Chan AffiliationsProgram in Moleular Medicine
KeywordsActivating Transcription Factor 2
Calcium-Calmodulin-Dependent Protein Kinases
Cyclic AMP Response Element-Binding Protein
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase 9
*Mitogen-Activated Protein Kinases
Molecular Sequence Data
Proto-Oncogene Proteins c-jun
Sequence Homology, Amino Acid
ets-Domain Protein Elk-1
Medicine and Health Sciences
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AbstractThe JNK protein kinase is a member of the MAP kinase group that is activated in response to dual phosphorylation on threonine and tyrosine. Ten JNK isoforms were identified in human brain by molecular cloning. These protein kinases correspond to alternatively spliced isoforms derived from the JNK1, JNK2 and JNK3 genes. The protein kinase activity of these JNK isoforms was measured using the transcription factors ATF2, Elk-1 and members of the Jun family as substrates. Treatment of cells with interleukin-1 (IL-1) caused activation of the JNK isoforms. This activation was blocked by expression of the MAP kinase phosphatase MKP-1. Comparison of the binding activity of the JNK isoforms demonstrated that the JNK proteins differ in their interaction with ATF2, Elk-1 and Jun transcription factors. Individual members of the JNK group may therefore selectively target specific transcription factors in vivo.
SourceEMBO J. 1996 Jun 3;15(11):2760-70.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/42129
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Molecular determinants that mediate selective activation of p38 MAP kinase isoformsEnslen, Herve; Brancho, Deborah Marie; Davis, Roger J. (2000-03-16)The p38 mitogen-activated protein kinase (MAPK) group is represented by four isoforms in mammals (p38alpha, p38beta2, p38gamma and p38delta). These p38 MAPK isoforms appear to mediate distinct functions in vivo due, in part, to differences in substrate phosphorylation by individual p38 MAPKs and also to selective activation by MAPK kinases (MAPKKs). Here we report the identification of two factors that contribute to the specificity of p38 MAPK activation. One mechanism of specificity is the selective formation of functional complexes between MAPKK and different p38 MAPKs. The formation of these complexes requires the presence of a MAPK docking site in the N-terminus of the MAPKK. The second mechanism that confers signaling specificity is the selective recognition of the activation loop (T-loop) of p38 MAPK isoforms. Together, these processes provide a mechanism that enables the selective activation of p38 MAPK in response to activated MAPKK.
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