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Citations to this article

Proteasomal regulation of βc signaling reveals a novel mechanism for cytokine receptor heterotypic desensitization
Margarita Martinez-Moczygemba, David P. Huston
Margarita Martinez-Moczygemba, David P. Huston
Published December 15, 2001
Citation Information: J Clin Invest. 2001;108(12):1797-1806. https://doi.org/10.1172/JCI13877.
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Article

Proteasomal regulation of βc signaling reveals a novel mechanism for cytokine receptor heterotypic desensitization

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Abstract

IL-5, IL-3, and GM-CSF are hematopoietic cytokines that are key mediators of the allergic inflammatory response. The receptors for these three cytokines consist of a cytokine-specific α (Rα) chain and a shared common β (βc) chain. Herein, we demonstrate that agonistic ligation of these receptor subunits rapidly induces proteasomal degradation of the βc, but not the Rα, cytoplasmic domain, resulting in termination of signal transduction and yielding a truncated βc isoform ligated to the Rα subunit. Proteasomal degradation of the βc cytoplasmic domain was also a prerequisite for endocytosis and lysosomal degradation of the ligated receptor subunits. Moreover, proteasome-dependent termination of signaling induced by one βc-engaging cytokine resulted in cellular desensitization to signal transduction by subsequent stimulation with another βc-engaging cytokine. These data provide the first evidence for ligand-dependent proteasomal degradation of the βc cytoplasmic domain, and they establish a novel mechanism for heterotypic desensitization of shared cytokine receptor signaling.

Authors

Margarita Martinez-Moczygemba, David P. Huston

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Total citations by year

Year: 2022 2020 2019 2016 2013 2012 2011 2010 2008 2005 Total
Citations: 1 1 1 1 3 1 2 1 3 1 15
Citation information
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Citations to this article in year 2016 (1)

Title and authors Publication Year
LNK/SH2B3 Loss of Function Promotes Atherosclerosis and ThrombosisNovelty and Significance
W Wang, Y Tang, Y Wang, L Tascau, J Balcerek, W Tong, RL Levine, C Welch, AR Tall, N Wang
Circulation research 2016

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