| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
The Journal of Immunology, Vol 158, Issue 12 5860-5867, Copyright © 1997 by American Association of Immunologists
ARTICLES |
M Reichel, BH Nelson, PD Greenberg and PB Rothman
Department of Dermatology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
The common gamma-chain (gamma(c)) is a functional component of the IL- 4R, yet cells lacking gamma(c) are able to respond to IL-4. This has led to the suggestion that a surrogate gamma'-chain, which can interact with the IL-4R alpha chain to mediate signaling, is expressed on cells lacking gamma(c). An alternative possibility is that in the absence of gamma(c), the IL-4R alpha chain is able to transduce signals by homodimerization. To test this latter possibility, a chimeric receptor containing the extracellular domain of c-kit (the stem cell factor (SCF) receptor) and the cytoplasmic and transmembrane domains of the IL- 4R alpha chain was generated. Treatment of cells expressing the chimeric receptor kit/IL-4R alpha with SCF induces activation of the IL- 4R alpha-associated kinase JAK-1 and the transcription factor STAT6. However, tyrosine phosphorylation of JAK-3, which associates with gamma(c), is not induced by SCF in these cells. SCF-mediated ligation of kit/IL-4R alpha is sufficient to elicit IL-4-specific gene expression, including up-regulation of CD23 and synthesis of germ-line epsilon transcripts. In the T cell line CTLL2, ligation of kit/IL-4R alpha induces cellular proliferation. Finally, in JAK-1-deficient HeLa cells, STAT6 activation by IL-4 is completely abolished. Together, these data demonstrate that the IL-4R alpha cytoplasmic domain is sufficient to activate JAK-1 and STAT6 and to induce expression of IL-4 target genes, thus identifying a mechanism by which IL-4 signaling can proceed in the absence of JAK-3 and gamma(c).
This article has been cited by other articles:
|
|
 |
|
  F. Ishikawa, M. Yasukawa, B. Lyons, S. Yoshida, T. Miyamoto, G. Yoshimoto, T. Watanabe, K. Akashi, L. D. Shultz, and M. Harada Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chainnull mice Blood, September 1, 2005; 106(5): 1565 - 1573. [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]
|
|
|
|
 |
|
 K. Kawakami, M. Kawakami, S. R. Husain, and R. K. Puri Effect of Interleukin (IL)-4 Cytotoxin on Breast Tumor Growth after in Vivo Gene Transfer of IL-4 Receptor {alpha} Chain Clin. Cancer Res., May 1, 2003; 9(5): 1826 - 1836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Roy, A. Bhattacharjee, B. Xu, D. Ford, A. L. Maizel, and M. K. Cathcart IL-13 signal transduction in human monocytes: phosphorylation of receptor components, association with Jaks, and phosphorylation/activation of Stats J. Leukoc. Biol., September 1, 2002; 72(3): 580 - 589. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Fukuda, Y. Fujitsu, N. Kumagai, and T. Nishida Characterization of the Interleukin-4 Receptor Complex in Human Corneal Fibroblasts Invest. Ophthalmol. Vis. Sci., January 1, 2002; 43(1): 183 - 188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Matsukura, C. Stellato, S. N. Georas, V. Casolaro, J. R. Plitt, K. Miura, S. Kurosawa, U. Schindler, and R. P. Schleimer Interleukin-13 Upregulates Eotaxin Expression in Airway Epithelial Cells by a STAT6-Dependent Mechanism Am. J. Respir. Cell Mol. Biol., June 1, 2001; 24(6): 755 - 761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. Tekkanat, H. F. Maassab, D. S. Cho, J. J. Lai, A. John, A. Berlin, M. H. Kaplan, and N. W. Lukacs IL-13-Induced Airway Hyperreactivity During Respiratory Syncytial Virus Infection Is STAT6 Dependent J. Immunol., March 1, 2001; 166(5): 3542 - 3548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jiang, K. Foltenyi, M. Kashiwada, L. Donahue, B. Vuong, B. Hehn, and P. Rothman Fes Mediates the IL-4 Activation of Insulin Receptor Substrate-2 and Cellular Proliferation J. Immunol., February 15, 2001; 166(4): 2627 - 2634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Suzuki, H. Nakajima, N. Watanabe, S.-i. Kagami, A. Suto, Y. Saito, T. Saito, and I. Iwamoto Role of common cytokine receptor gamma chain (gamma c)- and Jak3-dependent signaling in the proliferation and survival of murine mast cells Blood, September 15, 2000; 96(6): 2172 - 2180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Baetta, M. Soma, C. De-Fraja, C. Comparato, C. Teruzzi, L. Magrassi, and E. Cattaneo Upregulation and Activation of Stat6 Precede Vascular Smooth Muscle Cell Proliferation in Carotid Artery Injury Model Arterioscler. Thromb. Vasc. Biol., April 1, 2000; 20(4): 931 - 939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Gupta, M. Jiang, and A. B. Pernis IFN-{alpha} Activates Stat6 and Leads to the Formation of Stat2:Stat6 Complexes in B Cells J. Immunol., October 1, 1999; 163(7): 3834 - 3841. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. C. Morse III, T. McCarty, N. A. Giese, L. Taddesse-Heath, and M. J. Grusby STAT6-Deficient Mice Exhibit Normal Induction of Murine AIDS and Expression of Immunoglobulin E following Infection with LP-BM5 Murine Leukemia Viruses J. Virol., August 1, 1999; 73(8): 7093 - 7095. [Abstract] [Full Text]
|
|
|
|
|
|
J. A. Losman, X. P. Chen, D. Hilton, and P. Rothman Cutting Edge: SOCS-1 Is a Potent Inhibitor of IL-4 Signal Transduction J. Immunol., April 1, 1999; 162(7): 3770 - 3774. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Mitsuyasu, Y. Yanagihara, X.-Q. Mao, P.-S. Gao, Y. Arinobu, K. Ihara, A. Takabayashi, T. Hara, T. Enomoto, S. Sasaki, et al. Cutting Edge: Dominant Effect of Ile50Val Variant of the Human IL-4 Receptor {alpha}-Chain in IgE Synthesis J. Immunol., February 1, 1999; 162(3): 1227 - 1231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. N. Georas, J. E. Cumberland, T. F. Burke, R. Chen, U. Schindler, and V. Casolaro Stat6 Inhibits Human Interleukin-4 Promoter Activity in T Cells Blood, December 15, 1998; 92(12): 4529 - 4538. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Marshall, M. J. Hansbury, B. J. Bolognese, R. J. Gum, P. R. Young, and R. J. Mayer Inhibitors of the p38 Mitogen-Activated Kinase Modulate IL-4 Induction of Low Affinity IgE Receptor (CD23) in Human Monocytes J. Immunol., December 1, 1998; 161(11): 6005 - 6013. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Lu, C. Ebensperger, Z. Dembic, Y. Wang, M. Kvatyuk, T. Lu, R. L. Coffman, S. Pestka, and P. B. Rothman Targeted disruption of the interferon-gamma receptor 2 gene results in severe immune defects in mice PNAS, July 7, 1998; 95(14): 8233 - 8238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Bonder, H. L. Dickensheets, J. J. Finlay-Jones, R. P. Donnelly, and P. H. Hart Involvement of the IL-2 Receptor {gamma}-Chain ({gamma}c) in the Control by IL-4 of Human Monocyte and Macrophage Proinflammatory Mediator Production J. Immunol., April 15, 1998; 160(8): 4048 - 4056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Giallourakis, M. Kashiwada, P.-Y. Pan, N. Danial, H. Jiang, J. Cambier, K. M. Coggeshall, and P. Rothman Positive Regulation of Interleukin-4-mediated Proliferation by the SH2-containing Inositol-5'-phosphatase J. Biol. Chem., September 15, 2000; 275(38): 29275 - 29282. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
