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Publication
A Protein Scaffold Coordinates SRC-Mediated JNK Activation in Response to
Metabolic Stress.
Authors Kant S, Standen CL, Morel C, Jung DY, Kim JK, Swat W, Flavell RA, Davis RJ
Submitted By Submitted Externally on 11/9/2017
Status Published
Journal Cell reports
Year 2017
Date Published 9/1/2017
Volume : Pages 20 : 2775 - 2783
PubMed Reference 28930674
Abstract Obesity is a major risk factor for the development of metabolic syndrome and
type 2 diabetes. How obesity contributes to metabolic syndrome is unclear. Free
fatty acid (FFA) activation of a non-receptor tyrosine kinase (SRC)-dependent
cJun NH2-terminal kinase (JNK) signaling pathway is implicated in this process.
However, the mechanism that mediates SRC-dependent JNK activation is unclear.
Here, we identify a role for the scaffold protein JIP1 in SRC-dependent JNK
activation. SRC phosphorylation of JIP1 creates phosphotyrosine interaction
motifs that bind the SH2 domains of SRC and the guanine nucleotide exchange
factor VAV. These interactions are required for SRC-induced activation of VAV
and the subsequent engagement of a JIP1-tethered JNK signaling module. The JIP1
scaffold protein, therefore, plays a dual role in FFA signaling by coordinating
upstream SRC functions together with downstream effector signaling by the JNK
pathway.




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