Role of the JIP4 scaffold protein in the regulation of mitogen-activated protein kinase signaling pathways.
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.
Kelkar
Nyaya
N
Howard Hughes Medical Institute, Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation St., Worcester, MA 01605, USA.
Standen
Claire L
CL
Davis
Roger J
RJ
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D004789:Enzyme Activation; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D016547:Kinesins; D048371:MAP Kinase Kinase 3 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D048669:MAP Kinase Kinase 6 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D048688:MAP Kinase Kinase 7 / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11
D048868:Adaptor Proteins, Signal Transducing; D048031:JNK Mitogen-Activated Protein Kinases; D016547:Kinesins; D048371:MAP Kinase Kinase 3; D048669:MAP Kinase Kinase 6; D048688:MAP Kinase Kinase 7; D020930:MAP Kinase Kinase Kinases; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D048051:p38 Mitogen-Activated Protein Kinases; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11; C403619:Mapk8ip3 protein, mouse; C468928:Spag9 protein, mouse; C482531:Map2k3 protein, mouse; C482567:Map2k6 protein, mouse; C482570:Map2k7 protein, mouse