Interaction of a mitogen-activated protein kinase signaling module with the neuronal protein JIP3
UMass Chan AffiliationsHoward Hughes Medical Institute, Program in Molecular Medicine
Keywords*Adaptor Proteins, Signal Transducing
Amino Acid Sequence
Embryonic and Fetal Development
*Gene Expression Regulation, Developmental
JNK Mitogen-Activated Protein Kinases
MAP Kinase Kinase Kinases
Mitogen-Activated Protein Kinases
Molecular Sequence Data
Nerve Tissue Proteins
Sequence Homology, Amino Acid
Medicine and Health Sciences
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AbstractThe c-Jun NH(2)-terminal kinase (JNK) group of mitogen-activated protein kinases (MAPKs) is activated in response to the treatment of cells with inflammatory cytokines and by exposure to environmental stress. JNK activation is mediated by a protein kinase cascade composed of a MAPK kinase and a MAPK kinase kinase. Here we describe the molecular cloning of a putative molecular scaffold protein, JIP3, that binds the protein kinase components of a JNK signaling module and facilitates JNK activation in cultured cells. JIP3 is expressed in the brain and at lower levels in the heart and other tissues. Immunofluorescence analysis demonstrated that JIP3 was present in the cytoplasm and accumulated in the growth cones of developing neurites. JIP3 is a member of a novel class of putative MAPK scaffold proteins that may regulate signal transduction by the JNK pathway.
SourceMol Cell Biol. 2000 Feb;20(3):1030-43.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/38572
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A mammalian scaffold complex that selectively mediates MAP kinase activationWhitmarsh, Alan J.; Cavanagh, Julie; Tournier, Cathy; Yasuda, Jun; Davis, Roger J. (1998-09-11)The 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.
Role of the JIP4 scaffold protein in the regulation of mitogen-activated protein kinase signaling pathwaysKelkar, Nyaya; Standen, Claire L.; Davis, Roger J. (2005-03-16)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.
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.