| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of Medicine and Microbiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032
Immunoreceptor tyrosine-based inhibitory motifs (ITIM) have been
implicated in the negative modulation of immunoreceptor signaling
pathways. The IL-4R 
-chain (IL-4R) contains a putative ITIM in
the carboxyl terminal. To determine the role of ITIM in the IL-4
signaling pathway, we ablated the ITIM of IL-4R by deletion and
site-directed mutagenesis and stably expressed the wild-type (WT) and
mutant hIL-4R in 32D/insulin receptor substrate-2 (IRS-2) cells.
Strikingly, 32D/IRS-2 cells expressing mutant human (h)IL-4R were
hyperproliferative in response to IL-4 compared with cells expressing
WT hIL-4R. Enhanced tyrosine phosphorylation of Stat6, but not
IRS-2, induced by hIL-4 was observed in cells expressing mutant Y713F.
Using peptides corresponding to the ITIM of hIL-4R, we demonstrate
that tyrosine-phosphorylated peptides, but not their nonphosphorylated
counterparts, coprecipitate SH2-containing tyrosine phosphatase-1,
SH2-containing tyrosine phosphatase-2, and SH2-containing inositol
5'-phosphatase. The in vivo association of SH2-containing inositol
5'-phosphatase with IL-4R was verified by coimmunoprecipitation with
anti-IL-4R Abs. These results demonstrate a functional role for
ITIM in the regulation of IL-4-induced
proliferation.
This article has been cited by other articles:
|
|
 |
|
  S. Y. Oh, T. Zheng, Y.-K. Kim, L. Cohn, R. J. Homer, A. N. J. McKenzie, and Z. Zhu A Critical Role of SHP-1 in Regulation of Type 2 Inflammation in the Lung Am. J. Respir. Cell Mol. Biol., May 1, 2009; 40(5): 568 - 574. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pouliot, P. Camateros, D. Radzioch, B. N. Lambrecht, and M. Olivier Protein Tyrosine Phosphatases Regulate Asthma Development in a Murine Asthma Model J. Immunol., February 1, 2009; 182(3): 1334 - 1340. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. H. Boekhoudt, M. R. Frazier-Jessen, and G. M. Feldman Immune complexes suppress IFN-{gamma} signaling by activation of the Fc{gamma}RI pathway J. Leukoc. Biol., April 1, 2007; 81(4): 1086 - 1092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Imhof, A.-S. Wavreille, A. May, M. Zacharias, S. Tridandapani, and D. Pei Sequence Specificity of SHP-1 and SHP-2 Src Homology 2 Domains: CRITICAL ROLES OF RESIDUES BEYOND THE pY+3 POSITION J. Biol. Chem., July 21, 2006; 281(29): 20271 - 20282. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Kuemmerle Occupation of {alpha}vbeta3-integrin by endogenous ligands modulates IGF-I receptor activation and proliferation of human intestinal smooth muscle Am J Physiol Gastrointest Liver Physiol, June 1, 2006; 290(6): G1194 - G1202. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Stephenson, D.-S. Park, A. L. Mora, S. Goenka, and M. Boothby Sequence Motifs in IL-4R{alpha} Mediating Cell-Cycle Progression of Primary Lymphocytes J. Immunol., October 15, 2005; 175(8): 5178 - 5185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wormald and D. J. Hilton Inhibitors of Cytokine Signal Transduction J. Biol. Chem., January 9, 2004; 279(2): 821 - 824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Blaeser, P. J. Bryce, N. Ho, V. Raman, F. Dedeoglu, D. D. Donaldson, R. S. Geha, H. C. Oettgen, and T. A. Chatila Targeted Inactivation of the IL-4 Receptor {alpha} Chain I4R Motif Promotes Allergic Airway Inflammation J. Exp. Med., October 20, 2003; 198(8): 1189 - 1200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Kelly-Welch, E. M. Hanson, M. R. Boothby, and A. D. Keegan Interleukin-4 and Interleukin-13 Signaling Connections Maps Science, June 6, 2003; 300(5625): 1527 - 1528. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
