TY - JOUR
T1 - Critical cytoplasmic domains of human interleukin-9 receptor α chain in interleukin-9-mediated cell proliferation and signal transduction
AU - Zhu, Yuan Xiao
AU - Sun, Hui Bin
AU - Tsang, Monica Lik Shing
AU - McMahel, Jon
AU - Grigsby, Susan
AU - Yin, Tinggui
AU - Yang, Yu Chung
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1997/8/22
Y1 - 1997/8/22
N2 - Interleukin-9 receptor (IL-9R) complex consists of a ligand-specific α chain and IL-2R γ chain. In this study, two regions in the cytoplasmic domain of human IL-9Rα were found to be important for IL-9-mediated cell growth. A membrane-proximal region that contains the BOX1 consensus sequence is required for IL-9-induced cell proliferation and tyrosine phosphorylation of Janus kinases (JAKs). Deletion of this region or internal deletion of the BOX1 motif abrogated IL-9-induced cell proliferation and signal transduction. However, substitution of the Pro-X-Pro in the BOX1 motif with Ala-X-Ala failed to abolish IL-9-induced cell proliferation but decreased IL-9-mediated tyrosine phosphorylation of JAK kinases, insulin receptor substrate-2, and signal transducer and activator of transcription 3 (STAT3) and expression of c-myc and junB. Another important region is downstream of the BOX1 motif and contains a STAT3 binding motif YLPQ. Deletion of this region significantly impaired IL-9-induced cell growth, activation of JAK kinases, insulin receptor substrate-2, and STAT3 and expression of early response genes. A point mutation changing YLPQ into YLPA greatly reduced IL-9-induced activation of STAT3 and expression of c-myc but did not affect cell proliferation. These results suggest that cooperation or cross-talk of signaling molecules associated with different domains of IL-9Rα other than STAT3 is essential for IL-9-mediated cell growth.
AB - Interleukin-9 receptor (IL-9R) complex consists of a ligand-specific α chain and IL-2R γ chain. In this study, two regions in the cytoplasmic domain of human IL-9Rα were found to be important for IL-9-mediated cell growth. A membrane-proximal region that contains the BOX1 consensus sequence is required for IL-9-induced cell proliferation and tyrosine phosphorylation of Janus kinases (JAKs). Deletion of this region or internal deletion of the BOX1 motif abrogated IL-9-induced cell proliferation and signal transduction. However, substitution of the Pro-X-Pro in the BOX1 motif with Ala-X-Ala failed to abolish IL-9-induced cell proliferation but decreased IL-9-mediated tyrosine phosphorylation of JAK kinases, insulin receptor substrate-2, and signal transducer and activator of transcription 3 (STAT3) and expression of c-myc and junB. Another important region is downstream of the BOX1 motif and contains a STAT3 binding motif YLPQ. Deletion of this region significantly impaired IL-9-induced cell growth, activation of JAK kinases, insulin receptor substrate-2, and STAT3 and expression of early response genes. A point mutation changing YLPQ into YLPA greatly reduced IL-9-induced activation of STAT3 and expression of c-myc but did not affect cell proliferation. These results suggest that cooperation or cross-talk of signaling molecules associated with different domains of IL-9Rα other than STAT3 is essential for IL-9-mediated cell growth.
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U2 - 10.1074/jbc.272.34.21334
DO - 10.1074/jbc.272.34.21334
M3 - Article
C2 - 9261146
AN - SCOPUS:0000886511
SN - 0021-9258
VL - 272
SP - 21334
EP - 23140
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 34
ER -