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 Email this article to a friend 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 Krishnan, K. Articles by Krolewski, J. J. Search for Related Content PubMed PubMed Citation Articles by Krishnan, K. Articles by Krolewski, J. J. Social Bookmarking                      What's this?

J Biol Chem, Vol. 273, Issue 31, 19495-19501, July 31, 1998

Identification of Amino Acid Residues Critical for the Src-homology 2 Domain-dependent Docking of Stat2 to the Interferon  Receptor

From the Department of Pathology and Irving Cancer Center, Columbia University, College of Physicians & Surgeons, New York, New York 10032

The interaction between Src-homology 2 domains (SH2) domains and phosphorylated tyrosine residues serves a critical role in intracellular signaling. In addition to the phosphotyrosine, adjacent residues are critical mediators of the specificity of this interaction. Upon treatment of cells with interferon  (IFN), the IFNaR1 subunit of the IFN receptor becomes tyrosine phosphorylated at position 466. The region surrounding phosphorylated tyrosine 466 subsequently acts as a docking site for the SH2 domain of Stat2, facilitating phosphorylation of the latter and, thus, the transduction of the IFN signal. In this report site-specific mutagenesis was employed to analyze the nature of the interaction between the SH2 domain of Stat2 and the region surrounding tyrosine 466 on IFNaR1. Mutation of the valine at the +1 position carboxyl-terminal to tyrosine 466 or of the serine at the +5 position inhibits the association of Stat2 with phosphorylated IFNaR1. Moreover, receptors mutated at either of these two positions act in a dominant manner to decrease IFN signaling, as assayed by both Stat2 phosphorylation and expression of an IFN-responsive reporter. The demonstration that these two residues are critical in mediating the interaction between Stat2 and IFNaR1 suggests that STAT proteins might utilize a structurally distinct subset of SH2 domains to mediate signal transduction from the cell surface to the nucleus.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				S.-Z. Wang and R. M. Roberts Interaction of Stress-Activated Protein Kinase-Interacting Protein-1 with the Interferon Receptor Subunit IFNAR2 in Uterine Endometrium Endocrinology, December 1, 2004; 145(12): 5820 - 5831. [Abstract] [Full Text] [PDF]

				L. Dumoutier, A. Tounsi, T. Michiels, C. Sommereyns, S. V. Kotenko, and J.-C. Renauld Role of the Interleukin (IL)-28 Receptor Tyrosine Residues for Antiviral and Antiproliferative Activity of IL-29/Interferon-{lambda}1: SIMILARITIES WITH TYPE I INTERFERON SIGNALING J. Biol. Chem., July 30, 2004; 279(31): 32269 - 32274. [Abstract] [Full Text] [PDF]

				E. M. Kofoed, V. Hwa, B. Little, K. A. Woods, C. K. Buckway, J. Tsubaki, K. L. Pratt, L. Bezrodnik, H. Jasper, A. Tepper, et al. Growth Hormone Insensitivity Associated with a STAT5b Mutation N. Engl. J. Med., September 18, 2003; 349(12): 1139 - 1147. [Full Text] [PDF]

				V. S. Cull, P. A. Tilbrook, E. J. Bartlett, N. L. Brekalo, and C. M. James Type I interferon differential therapy for erythroleukemia: specificity of STAT activation Blood, April 1, 2003; 101(7): 2727 - 2735. [Abstract] [Full Text] [PDF]

				S. Velichko, T. C. Wagner, J. Turkson, R. Jove, and E. Croze STAT3 Activation by Type I Interferons Is Dependent on Specific Tyrosines Located in the Cytoplasmic Domain of Interferon Receptor Chain 2c. ACTIVATION OF MULTIPLE STATS PROCEEDS THROUGH THE REDUNDANT USAGE OF TWO TYROSINE RESIDUES J. Biol. Chem., September 13, 2002; 277(38): 35635 - 35641. [Abstract] [Full Text] [PDF]

				V.-P. Nguyen, A. Z. M. Saleh, A. E. Arch, H. Yan, F. Piazza, J. Kim, and J. J. Krolewski Stat2 Binding to the Interferon-alpha Receptor 2 Subunit Is Not Required for Interferon-alpha Signaling J. Biol. Chem., March 15, 2002; 277(12): 9713 - 9721. [Abstract] [Full Text] [PDF]

				D. Russell-Harde, T. C. Wagner, M. R. S. Rani, D. Vogel, O. Colamonici, R. M. Ransohoff, B. Majchrzak, E. Fish, H. D. Perez, and E. Croze Role of the Intracellular Domain of the Human Type I Interferon Receptor 2 Chain (IFNAR2c) in Interferon Signaling. EXPRESSION OF IFNAR2c TRUNCATION MUTANTS IN U5A CELLS J. Biol. Chem., July 28, 2000; 275(31): 23981 - 23985. [Abstract] [Full Text] [PDF]