HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Related articles in The JI Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mora, A. L. Articles by Boothby, M. Search for Related Content PubMed PubMed Citation Articles by Mora, A. L. Articles by Boothby, M.

New Programming of IL-4 Receptor Signal Transduction in Activated T Cells: Stat6 Induction and Th2 Differentiation Mediated by IL-4R Lacking Cytoplasmic Tyrosines¹

Ana L. Mora^2,3,*, Linda M. Stephenson^2,*, Ben Enerson^*, Jeehee Youn^4,*, Achsah D. Keegan and Mark Boothby^5,*,

Departments of ^* Microbiology and Immunology and Medicine (Rheumatology), Vanderbilt University Medical School, Nashville, TN 37232; and Immunology Department, American Red Cross Holland Labs, Rockville, MD 20855

Signaling by the IL-4 receptor -chain (IL-4R) is a key determinant of the development of the Th2 lineage of effector T cells. Studies performed in tissue culture cell lines have indicated that tyrosines of the IL-4R cytoplasmic tail are necessary for the induction of Stat6, a transcription factor required for Th2 differentiation. Surprisingly, we have found that in activated T cells, IL-4R chains lacking all cytoplasmic tyrosines promote induction of this IL-4-specific transcription factor and efficient commitment to the Th2 lineage. Mutagenesis of a tyrosine-free cytoplasmic tail identifies a requirement for the serine-rich ID-1 region in this new program of IL-4R signal transduction observed in activated T cells. Additional findings suggest that an extracellular signal-regulated kinase pathway can be necessary and sufficient for the ability of such tyrosine-free IL-4R chains to mediate Stat6 induction. These results provide novel evidence that the molecular mechanisms by which a cytokine specifically induces a Stat transcription factor can depend on the activation state of T lymphoid cells. Furthermore, the data suggest that one pathway by which such new programming may be achieved is mediated by extracellular signal-regulated mitogen-activated protein kinases.

Related articles in The JI:

IN THIS ISSUE

The JI 2003 171: 1619-1620. [Full Text]  

This article has been cited by other articles:

				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]

				A. Kelly-Welch, E. M. Hanson, and A. D. Keegan Interleukin-4 (IL-4) Pathway Sci. Signal., July 19, 2005; 2005(293): cm9 - cm9. [Abstract] [Full Text] [PDF]

				Y. Tong, T. Aune, and M. Boothby T-bet antagonizes mSin3a recruitment and transactivates a fully methylated IFN-{gamma} promoter via a conserved T-box half-site PNAS, February 8, 2005; 102(6): 2034 - 2039. [Abstract] [Full Text] [PDF]