GRASP-1 is a neuronal scaffold protein for the JNK signaling pathway

Bing Ye, Wei ping Yu, Gareth M. Thomas, Richard L. Huganir

Research output: Contribution to journalArticle


GRASP-1 is a neuronally enriched protein that interacts with the AMPA-type glutamate receptor/GRIP complex. GRASP-1 can be cleaved by Caspase-3 in both normal and ischemic brains although the functional significance of this cleavage remains elusive. We investigated signal transduction pathways that might lie downstream of GRASP-1 and found that GRASP-1 potently activates JNK pathway signaling, with no effect on ERK signaling. Such JNK pathway activating activity requires binding of GRASP-1 to both JNK and the upstream JNK pathway activator MEKK-1. Furthermore, mutations that prevent Caspase 3-cleavage of GRASP-1 dramatically inhibit the JNK pathway activating activity of GRASP-1, suggesting a novel link between Caspase-3 activation and JNK pathway signaling. These results suggest that GRASP-1 serves as a scaffold protein to facilitate MEKK-1 activation of JNK signaling in neurons.

Original languageEnglish (US)
Pages (from-to)4403-4410
Number of pages8
JournalFEBS Letters
Issue number23
StatePublished - Sep 18 2007


  • Caspase
  • GRIP
  • MEKK-1

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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