Role of the JIP4 scaffold protein in the regulation of mitogen-activated protein kinase signaling pathways

Mol Cell Biol. 2005 Apr;25(7):2733-43. doi: 10.1128/MCB.25.7.2733-2743.2005.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cells, Cultured
  • Chlorocebus aethiops
  • Cloning, Molecular
  • Cytoplasm / metabolism
  • Enzyme Activation
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Kinesins
  • MAP Kinase Kinase 3 / deficiency
  • MAP Kinase Kinase 3 / genetics
  • MAP Kinase Kinase 3 / metabolism
  • MAP Kinase Kinase 6 / deficiency
  • MAP Kinase Kinase 6 / genetics
  • MAP Kinase Kinase 6 / metabolism
  • MAP Kinase Kinase 7 / metabolism
  • MAP Kinase Kinase Kinases / metabolism
  • MAP Kinase Signaling System*
  • Mice
  • Mice, Knockout
  • Microtubule-Associated Proteins / metabolism
  • Mitogen-Activated Protein Kinase Kinase Kinase 11
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Phosphorylation
  • Protein Binding
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Mapk8ip3 protein, mouse
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Spag9 protein, mouse
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases
  • MAP Kinase Kinase 3
  • MAP Kinase Kinase 6
  • MAP Kinase Kinase 7
  • Map2k3 protein, mouse
  • Map2k6 protein, mouse
  • Map2k7 protein, mouse
  • Kinesins