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An essential role of the JIP1 scaffold protein for JNK activation in adipose tissue
Open accessAbstract
The c-Jun NH 2-terminal kinase (JNK) is activated during obesity. One consequence of obesity is that JNK phosphorylates the adapter protein insulin receptor substrate 1 (IRS-1) on Ser 307 and inhibits signaling by the insulin receptor. JNK can therefore cause peripheral insulin resistance during obesity and may contribute to the development of type 2 diabetes. Here we report that the JNK-interacting protein 1 (JIP1) scaffold protein, which binds components of the JNK signaling module, is essential for JNK activation in the adipose tissue of obese mice. These data identify JIP1 as a novel molecular target for therapeutic intervention in the development of obesity.
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“JIP1 is a cytoplasmic scaffold protein that interacts with the upstream activating kinases for JNK, and is required for activity in a number of different contexts, including regulation of obesity-induced insulin resistance (Jaeschke et al., 2004; Morel et al., 2010; Weston and Davis, 2007; Whitmarsh et al., 2001).”
From Structural Mechanisms of Allostery and Autoinhibition in JNK Family Kinases (2012) · cites this paper as Jaeschke et al., 2004
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“However, it is now clear from more physiologically relevant studies that JIP1 is required for activation of JNK (Jaeschke et al., 2004; Morel et al., 2010; Whitmarsh et al., 2001), and is only inhibitory when overexpressed.”
From Structural Mechanisms of Allostery and Autoinhibition in JNK Family Kinases (2012) · cites this paper as Jaeschke et al., 2004
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Metadata
- Authors
- Jaeschke, A., Czech, M. P., & Davis, R. J.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2004-08-15
- Volume
- 18
- Issue
- 16
- Pages
- 1976-1980
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC514178
- OpenAlex
- W2156584134
- Cited by
- 121
- References
- 26
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 6 · 2019: 5 · 2018: 6 · 2017: 5 · 2016: 6 · 2015: 4 · 2014: 2 · 2013: 5 · 2012: 3
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- JIP1, JNK activation, c-Jun NH2-terminal kinase, adipose tissue, obesity, insulin resistance, IRS-1, type 2 diabetes, scaffold proteins
- MeSH terms
- Adipose Tissue, Animals, Diet, Enzyme Activation, Insulin Resistance, Mice, Inbred C57BL, Nuclear Proteins, Trans-Activators, Mitogen-Activated Protein Kinase Kinases, JNK Mitogen-Activated Protein Kinases, MAP Kinase Kinase 4, Adaptor Proteins, Signal Transducing, Mice
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