Cited by 122Adipokines, Inflammation, and Metabolic DiseasesProtein Tyrosine PhosphatasesMetabolism, Diabetes, and Cancer

An essential role of the JIP1 scaffold protein for JNK activation in adipose tissue

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Jaeschke, Anja, Czech, Michael P., Davis, Roger J.·2004·Genes & Development

Abstract

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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Crossref · 10.1101/gad.1216504

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  • JIP1 is a cytoplasmic scaffold that interacts with JNK-activating kinases and is needed for JNK activity in several settings, including obesity-induced insulin resistance.

    “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

  • More physiological studies show that JIP1 is required for JNK activation and is inhibitory only when overexpressed.

    “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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Authors
Jaeschke, A., Czech, M. P., & Davis, R. J.
Affiliations
Howard Hughes Medical Institute (US)
Venue
Genes & Development
Published
2004-08-15
Volume
18
Issue
16
Pages
1976-1980
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
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
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 › Epidemiology › 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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