Src family kinases directly regulate JIP1 module dynamics and activation

Mol Cell Biol. 2007 Apr;27(7):2431-41. doi: 10.1128/MCB.01479-06. Epub 2007 Jan 22.

Abstract

JIP1 is a mammalian scaffold protein that assembles and participates in regulating the dynamics and activation of components of the mixed-lineage kinase-dependent JNK module. Mechanisms governing JIP1-JNK module regulation remain unclear. JIP1 is a multiply phosphorylated protein; for this reason, it was hypothesized that signaling by unidentified protein kinases or phosphatases might determine module function. We find that Src family kinases directly bind and tyrosine phosphorylate JIP1 under basal conditions in several naturally occurring systems and, by doing so, appear to provide a regulated signal that increases the affinity of JIP1 for DLK and maintains the JIP-JNK module in a catalytically inactive state.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Amino Acids
  • Animals
  • Catalysis
  • Cell Line
  • MAP Kinase Kinase Kinases / metabolism
  • Mice
  • Molecular Sequence Data
  • Neurons / metabolism
  • Phosphorylation
  • Protein Binding
  • Proto-Oncogene Proteins c-fyn / genetics
  • Rats
  • src-Family Kinases / metabolism
  • src-Family Kinases / physiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Amino Acids
  • Mapk8ip protein, mouse
  • Fyn protein, mouse
  • Proto-Oncogene Proteins c-fyn
  • src-Family Kinases
  • MAP Kinase Kinase Kinases
  • mitogen-activated protein kinase kinase kinase 12