Role of the JIP4 scaffold protein in the regulation of mitogen-activated protein kinase signaling pathways
UMass Chan Affiliations
Howard Hughes Medical Institute, Program in Molecular MedicineDocument Type
Journal ArticlePublication Date
2005-03-16Keywords
Adaptor Proteins, Signal TransducingAnimals
Cells, Cultured
Cercopithecus aethiops
Cloning, Molecular
Cytoplasm
Enzyme Activation
JNK Mitogen-Activated Protein Kinases
MAP Kinase Kinase 3
MAP Kinase Kinase 6
MAP Kinase Kinase 7
MAP Kinase Kinase Kinases
*MAP Kinase Signaling System
Mice
Mice, Knockout
Microtubule-Associated Proteins
Nerve Tissue Proteins
Phosphorylation
Protein Binding
p38 Mitogen-Activated Protein Kinases
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
The c-Jun NH2-terminal kinase (JNK)-interacting protein (JIP) group of scaffold proteins (JIP1, JIP2, and JIP3) can interact with components of the JNK signaling pathway and potently activate JNK. Here we describe the identification of a fourth member of the JIP family. The primary sequence of JIP4 is most closely related to that of JIP3. Like other members of the JIP family of scaffold proteins, JIP4 binds JNK and also the light chain of the microtubule motor protein kinesin-1. However, the function of JIP4 appears to be markedly different from other JIP proteins. Specifically, JIP4 does not activate JNK signaling. In contrast, JIP4 serves as an activator of the p38 mitogen-activated protein (MAP) kinase pathway by a mechanism that requires the MAP kinase kinases MKK3 and MKK6. The JIP4 scaffold protein therefore appears to be a new component of the p38 MAP kinase signaling pathway.Source
Mol Cell Biol. 2005 Apr;25(7):2733-43. Link to article on publisher's siteDOI
10.1128/MCB.25.7.2733-2743.2005Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38545PubMed ID
15767678Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1128/MCB.25.7.2733-2743.2005
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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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Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6Enslen, Herve; Raingeaud, Joel; Davis, Roger J. (1998-01-27)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, p38 beta 2. This p38 MAP kinase, like p38 alpha, is inhibited by the pyridinyl imidazole drug SB203580. The p38 MAP kinase kinase MKK6 is identified as a common activator of p38 alpha, p38 beta 2, and p38 gamma MAP kinase isoforms, while MKK3 activates only p38 alpha and p38 gamma MAP kinase isoforms. The MKK3 and MKK6 signal transduction pathways are therefore coupled to distinct, but overlapping, groups of p38 MAP kinases.