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A Protein Scaffold Coordinates SRC-Mediated JNK Activation in Response to Metabolic Stress

Shashi Kant1, Claire L Standen2, Caroline Morel2

  • 1Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.

Cell Reports
|September 21, 2017
PubMed

Insights

Obesity contributes to metabolic syndrome via free fatty acids (FFAs) activating SRC and JNK signaling. The scaffold protein JIP1 is key, coordinating SRC and JNK pathways for FFA-induced metabolic dysfunction.

Area of Science:

  • Biochemistry
  • Cellular Biology
  • Metabolic Disease Research

Background:

  • Obesity is a significant risk factor for metabolic syndrome and type 2 diabetes.
  • The precise mechanisms linking obesity to metabolic syndrome are not fully understood.
  • Free fatty acid (FFA) activation of SRC-dependent c-Jun NH2-terminal kinase (JNK) signaling is implicated, but the activation mechanism is unclear.

Purpose of the Study:

  • To elucidate the mechanism of SRC-dependent JNK activation in the context of FFA signaling.
  • To identify the role of scaffold proteins in mediating this signaling pathway.

Main Methods:

  • Investigated the interaction between SRC, JIP1, and VAV.
  • Analyzed SRC-mediated phosphorylation of JIP1.
  • Examined the role of JIP1 in JNK pathway activation.

Main Results:

  • Identified JIP1 as a crucial scaffold protein in SRC-dependent JNK activation.
  • SRC phosphorylation of JIP1 creates binding sites for SRC and VAV.
  • These interactions facilitate SRC-induced VAV activation and JNK signaling module engagement.

Conclusions:

  • JIP1 plays a dual role in FFA signaling, coordinating upstream SRC activity and downstream JNK pathway effector functions.
  • This highlights JIP1 as a central mediator in the signaling cascade linking FFAs to metabolic dysfunction.
Keywords:
JIP1JNKfatty acidinsulin resistance

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