Signal Transduction and Intracellular Trafficking by the Interleukin 36 Receptor |
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Authors: | Siddhartha S Saha Divyendu Singh Ernest L Raymond Rajkumar Ganesan Gary Caviness Christine Grimaldi Joseph R Woska Jr Detlev Mennerich Su-Ellen Brown M Lamine Mbow C Cheng Kao |
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Institution: | From the ‡Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana 47401 and ;§Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877 |
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Abstract: | Improper signaling of the IL-36 receptor (IL-36R), a member of the IL-1 receptor family, has been associated with various inflammation-associated diseases. However, the requirements for IL-36R signal transduction remain poorly characterized. This work seeks to define the requirements for IL-36R signaling and intracellular trafficking. In the absence of cognate agonists, IL-36R was endocytosed and recycled to the plasma membrane. In the presence of IL-36, IL-36R increased accumulation in LAMP1+ lysosomes. Endocytosis predominantly used a clathrin-mediated pathway, and the accumulation of the IL-36R in lysosomes did not result in increased receptor turnover. The ubiquitin-binding Tollip protein contributed to IL-36R signaling and increased the accumulation of both subunits of the IL-36R. |
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Keywords: | endocytosis immunology IL-1 signal transduction trafficking interleukin 36 receptor Tollip |
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