Program in Molecular Medicine; Department of Medicine, Division of Cardiovascular Medicine; Department of Medicine, Division of Endocrinology, Metabolism and Diabetes; Davis Lab; UMass Metabolic Network
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Endocrinology | Molecular Biology
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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DOI of Published Version
Cell Rep. 2017 Sep 19;20(12):2775-2783. doi: 10.1016/j.celrep.2017.08.025. Link to article on publisher's site
Kant, Shashi; Standen, Claire L.; Morel, Caroline; Jung, Dae Young; Kim, Jason K.; Swat, Wojciech; Flavell, Richard A.; and Davis, Roger J., "A Protein Scaffold Coordinates SRC-Mediated JNK Activation in Response to Metabolic Stress" (2017). UMass Metabolic Network Publications. 166.
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