The interleukin-13 receptor alpha 2 chain: an essential component for binding and internalization but not for interleukin-13-induced signal transduction through the STAT6 pathway
K. Kawakami et al., The interleukin-13 receptor alpha 2 chain: an essential component for binding and internalization but not for interleukin-13-induced signal transduction through the STAT6 pathway, BLOOD, 97(9), 2001, pp. 2673-2679
The interleukin-13 receptor (IL-13R) complex is composed of 2 different cha
ins, IL-13R alpha1 (also known as IL-13R alpha') and IL-13R alpha2 (also kn
own as IL-13R alpha). For a functional IL-13 receptor, the IL-13R alpha1 ch
ain forms a productive complex with the primary IL-4 binding protein (IL-4R
alpha also known as IL-4R beta). However, the function of the IL-13R alpha
2 chain is not clear even though this chain binds IL-13 with high affinity.
This study demonstrates that IL-13R alpha2 can undergo internalization aft
er binding to ligand without causing activation of its signaling pathways.
These conclusions were drawn on the basis of (1) internalization of I-125-I
L-13 in Chinese hamster ovarian (CHO-K1) and T98G glioblastoma cells transi
ently transfected with the IL-13Ra2 chain; (2) a recombinant chimeric fusio
n protein comprising IL-13 and a mutated form of Pseudomonas exotoxin (term
ed IL13-PE38QQR or IL-13 toxin) is specifically cytotoxic to IL-13R alpha2-
transfected CHO-K1 cells in a gene dose-dependent manner, whereas cells tra
nsfected 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-13R alpha2-transfected cells. IL-13 efficiently caused activation of
STAT6 protein in cells transfected with the IL-13R alpha1 and IL-4R alpha
chains, and IL-13R alpha2 inhibited this activation. Taken together, these
observations indicate that internalization of IL-13R alpha2 is signal indep
endent and that this property of IL-13R alpha2 can be exploited for recepto
r-directed cancer therapy. (Blood, 2001;97:2673-2679) (C) 2001 by The Ameri
can Society of Hematology.