The interleukin-13 receptor alpha2 chain: an essential component for binding and internalization but not for interleukin-13-induced signal transduction through the STAT6 pathway.

Blood
Koji KawakamiRaj K Puri

Abstract

The interleukin-13 receptor (IL-13R) complex is composed of 2 different chains, IL-13Ralpha1 (also known as IL-13Ralpha') and IL-13Ralpha2 (also known as IL-13Ralpha). For a functional IL-13 receptor, the IL-13Ralpha1 chain forms a productive complex with the primary IL-4 binding protein (IL-4Ralpha also known as IL-4Rbeta). However, the function of the IL-13Ralpha2 chain is not clear even though this chain binds IL-13 with high affinity. This study demonstrates that IL-13Ralpha2 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 (125)I-IL-13 in Chinese hamster ovarian (CHO-K1) and T98G glioblastoma cells transiently transfected with the IL-13Ralpha2 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-13Ralpha2-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-13Ralpha2-transfected cells. IL-13 efficientl...Continue Reading

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