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Related Collections Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 May 2001, Vol. 97, No. 9, pp. 2673-2679 IMMUNOBIOLOGY The interleukin-13 receptor 2 chain: an essential component for binding and internalization but not for interleukin-13-induced signal transduction through the STAT6 pathway Koji Kawakami, Jun Taguchi, Takashi Murata, and Raj K. Puri From the Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, National Institutes of Health, Bethesda, MD. The interleukin-13 receptor (IL-13R) complex is composed of 2 different chains, IL-13R1 (also known as IL-13R') and IL-13R2 (also known as IL-13R). For a functional IL-13 receptor, the IL-13R1 chain forms a productive complex with the primary IL-4 binding protein (IL-4R also known as IL-4R). However, the function of the IL-13R2 chain is not clear even though this chain binds IL-13 with high affinity. This study demonstrates that IL-13R2 can undergo internalization after binding to ligand without causing activation of its signaling pathways. These conclusions were drawn on the basis of (1) internalization of 125I-IL-13 in Chinese hamster ovarian (CHO-K1) and T98G glioblastoma cells transiently transfected with the IL-13R2 chain; (2) a recombinant chimeric fusion protein comprising IL-13 and a mutated form of Pseudomonas exotoxin (termed IL13-PE38QQR or IL-13 toxin) is specifically cytotoxic to IL-13R2-transfected CHO-K1 cells in a gene dose-dependent manner, whereas cells transfected with vector alone were not sensitive; and (3) IL-13 did not cause activation of signal transduction and activation of transcription 6 (STAT6) in IL-13R2-transfected cells. IL-13 efficiently caused activation of STAT6 protein in cells transfected with the IL-13R1 and IL-4R chains, and IL-13R2 inhibited this activation. Taken together, these observations indicate that internalization of IL-13R2 is signal independent and that this property of IL-13R2 can be exploited for receptor-directed cancer therapy. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I Arijs, K Li, G Toedter, R Quintens, L Van Lommel, K Van Steen, P Leemans, G De Hertogh, K Lemaire, M Ferrante, et al. Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis Gut, December 1, 2009; 58(12): 1612 - 1619. [Abstract] [Full Text] [PDF] T. Fujisawa, B. Joshi, A. Nakajima, and R. K. Puri A Novel Role of Interleukin-13 Receptor {alpha}2 in Pancreatic Cancer Invasion and Metastasis Cancer Res., November 15, 2009; 69(22): 8678 - 8685. 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