UMMS Affiliation

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

Publication Date


Document Type



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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© 2017 The Author(s).

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

Journal/Book/Conference Title

Cell reports

Related Resources

Link to Article in PubMed

PubMed ID


Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.



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