The JIP group of mitogen-activated protein kinase scaffold proteins
UMass Chan Affiliations
Howard Hughes Medical Institute, Program in Molecular MedicineDocument Type
Journal ArticlePublication Date
1999-09-22Keywords
*Adaptor Proteins, Signal TransducingAmino Acid Sequence
Carrier Proteins
Cell Compartmentation
Cloning, Molecular
JNK Mitogen-Activated Protein Kinases
MAP Kinase Kinase 7
MAP Kinase Kinase Kinases
Mitogen-Activated Protein Kinase Kinases
Mitogen-Activated Protein KinasesMolecular Sequence DataProtein BindingProtein Structure, QuaternarySequence Homology, Amino AcidSignal TransductionLife SciencesMedicine and Health Sciences
Metadata
Show full item recordAbstract
Activation of the c-Jun NH(2)-terminal kinase (JNK) group of mitogen-activated protein (MAP) kinases is mediated by a protein kinase cascade. This signaling mechanism may be coordinated by the interaction of components of the protein kinase cascade with scaffold proteins. The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates signaling by the mixed-lineage kinase (MLK)-->MAP kinase kinase 7 (MKK7)-->JNK pathway. The scaffold proteins JIP1 and JIP2 interact to form oligomeric complexes that accumulate in peripheral cytoplasmic projections extended at the cell surface. The JIP proteins function by aggregating components of a MAP kinase module (including MLK, MKK7, and JNK) and facilitate signal transmission by the protein kinase cascade.Source
Mol Cell Biol. 1999 Oct;19(10):7245-54.Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38576PubMed ID
10490659Related Resources
Link to Article in PubMedCollections
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A mammalian scaffold complex that selectively mediates MAP kinase activationThe c-Jun NH2-terminal kinase (JNK) group of mitogen-activated protein (MAP) kinases is activated by the exposure of cells to multiple forms of stress. A putative scaffold protein was identified that interacts with multiple components of the JNK signaling pathway, including the mixed-lineage group of MAP kinase kinase kinases (MLK), the MAP kinase kinase MKK7, and the MAP kinase JNK. This scaffold protein selectively enhanced JNK activation by the MLK signaling pathway. These data establish that a mammalian scaffold protein can mediate activation of a MAP kinase signaling pathway.
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Molecular determinants that mediate selective activation of p38 MAP kinase isoformsThe 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.
