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dc.contributor.authorKant, Shashi
dc.contributor.authorStanden, Claire L.
dc.contributor.authorMorel, Caroline
dc.contributor.authorJung, Dae Young
dc.contributor.authorKim, Jason K.
dc.contributor.authorSwat, Wojciech
dc.contributor.authorFlavell, Richard A.
dc.contributor.authorDavis, Roger J.
dc.date2022-08-11T08:09:20.000
dc.date.accessioned2022-08-23T16:26:49Z
dc.date.available2022-08-23T16:26:49Z
dc.date.issued2017-09-19
dc.date.submitted2017-12-22
dc.identifier.citationCell Rep. 2017 Sep 19;20(12):2775-2783. doi: 10.1016/j.celrep.2017.08.025. <a href="https://doi.org/10.1016/j.celrep.2017.08.025">Link to article on publisher's site</a>
dc.identifier.issn2211-1247 (Electronic)
dc.identifier.doi10.1016/j.celrep.2017.08.025
dc.identifier.pmid28930674
dc.identifier.urihttp://hdl.handle.net/20.500.14038/36646
dc.description.abstractObesity 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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=28930674&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rights© 2017 The Author(s).
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectBiochemistry
dc.subjectCell Biology
dc.subjectCellular and Molecular Physiology
dc.subjectEndocrinology
dc.subjectMolecular Biology
dc.titleA Protein Scaffold Coordinates SRC-Mediated JNK Activation in Response to Metabolic Stress
dc.typeJournal Article
dc.source.journaltitleCell reports
dc.source.volume20
dc.source.issue12
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1173&amp;context=metnet_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/metnet_pubs/166
dc.identifier.contextkey11293388
refterms.dateFOA2022-08-23T16:26:50Z
html.description.abstract<p>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.</p>
dc.identifier.submissionpathmetnet_pubs/166
dc.contributor.departmentUMass Metabolic Network
dc.contributor.departmentDavis Lab
dc.contributor.departmentDepartment of Medicine, Division of Endocrinology, Metabolism and Diabetes
dc.contributor.departmentDepartment of Medicine, Division of Cardiovascular Medicine
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages2775-2783


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© 2017 The Author(s).
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