Cloning of a receptor subunit required for signaling by thymic stromal lymphopoietin.
Signaling by type I cytokines involves the formation of receptor homodimers, heterodimers or higher order receptor oligomers. Here we report the cloning of a type I cytokine receptor subunit that is most closely related to the common cytokine receptor gamma chain (gamma c). Binding and crosslinking experiments demonstrate that this protein is the receptor for a recently described interleukin 7 (IL-7)-like factor, thymic stromal lymphopoietin (TSLP). Binding of TSLP to the thymic stromal lymphopoietin receptor (TSLPR) is increased markedly in the presence of the IL-7 receptor alpha chain (IL-7R alpha). IL-7R alpha-expressing but not parental 32D cells proliferate in the presence of exogenous TSLP. Moreover, a combination of IL-7R alpha and TSLPR is required for TSLP-dependent activation of a STAT5-dependent reporter construct. Thus it is shown that IL-7R alpha is a component of both the IL-7 and TSLP receptors, which helps to explain why deletion of the gene that encodes IL-7R alpha affects the lymphoid system more severely than deletion of the gene encoding IL-7 does. Cloning of TSLPR should facilitate an understanding of TSLP function and its signaling mechanism.
Pandey
A
A
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Ozaki
K
K
Baumann
H
H
Levin
S D
SD
Puel
A
A
Farr
A G
AG
Ziegler
S F
SF
Leonard
W J
WJ
Lodish
H F
HF
D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D015851:Interleukin-7 / Q000276:immunology*; D008969:Molecular Sequence Data; D020395:Receptors, Interleukin-7 / Q000235:genetics* / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
D015851:Interleukin-7; D020395:Receptors, Interleukin-7