A novel member of the interferon receptor family complements functionality of the murine interferon γ receptor in human cells

Hemmi, Silvio; Böhni, Ruth; Stark, George Stark; Marco, Francesco Di; Aguet, Michel

doi:10.1016/0092-8674(94)90355-7

Cited by 199 publications

(98 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The common feature of the members of this family is the activation by homodimerization of two identical molecules [60][61][62]. [66,67]. The IL-10 receptor is structurally related to the interferon receptors [68].…”

Section: Il-2 Familymentioning

confidence: 99%

The Jak–STAT pathway: specific signal transduction from the cell membrane to the nucleus

Heim

1996

Eur J Clin Investigation

View full text Add to dashboard Cite

Abstract. The Jak-STAT pathway is a newly discovered intracellular signal transduction pathway that is used by a growing number of extracellular signalling proteins (ESPs) for transciptional activation of target genes. Binding of ligands to their transmembrane receptors leads to activation of members of the Jak tyrosine kinase family. The activated receptor-kinase complexes recruit members of the STAT family and activate them by phosphorylation. As a consequence, the phosphorylated STAT proteins dimerize, translocate into the nucleus, bind response elements in the promoter of target genes and stimulate the transcription of these genes. Their dual role as signalling molecules and transcription factors is reflected in the name: STAT stands for signal transducers and activators of transcription. Different ligands specifically activate different members of the Jak and STAT families. Signal transduction through the Jak-STAT pathway contributes to the specificity and diversity of cellular responses to peptide hormones, growth factors, cytokines and interleukins.

show abstract

Section: Il-2 Familymentioning

confidence: 99%

The Jak–STAT pathway: specific signal transduction from the cell membrane to the nucleus

Heim

1996

Eur J Clin Investigation

View full text Add to dashboard Cite

show abstract

“…This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. (30,32). cDNA encoding the murine Stat5a (33) was provided by Dr. Bernd Groner (Georg Speyer Institute, Frankfurt), and a murine Stat5b cDNA (34) was kindly provided by Dr. Chris Schindler (Columbia University, New York).…”

Section: Methodsmentioning

confidence: 99%

“…Cells, Transfection of Cells, Cytokines-COS7, COSN31 cells (30), 293HEK, and murine Stat1-deficient fibroblasts (31) were maintained in Dulbecco's modified Eagle's medium supplemented with 10% fetal calf serum. COS7 and COSN31 cells were transfected with indicated amounts of plasmids by electroporation.…”

Section: Methodsmentioning

confidence: 99%

“…Isoforms by the IFN-␥R-To determine whether the isoform-specific activation of Stat5 in the IFN-␥ response of macrophage progenitor cells results from an intrinsic ability of the IFN-␥R to discriminate between Stat5a and Stat5b, we transfected the murine IFNGR2 chain into COSN31 cells, which stably express the murine IFNGR1 chain (30), along with either Stat5a or Stat5b. The transfected cells were treated with murine IFN-␥, which binds specifically to the murine IFN-␥R of transfected cells.…”

Section: Activation Of Both Stat5mentioning

confidence: 99%

See 1 more Smart Citation

The Stat1 Binding Motif of the Interferon-γ Receptor Is Sufficient to Mediate Stat5 Activation and Its Repression by SOCS3

Woldman¹,

Varinou²,

Ramsauer

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…of a related receptor, IFN-yRpI, is required for signaling via the JAK/STAT pathway. IFN-yRpI is postulated to be one member of a family of accessory factors that allows for the different cellular responses of IFN-y (Soh et al, 1994;Hemmi et al, 1994).…”

mentioning

confidence: 99%

Crystallization and preliminary X‐ray analysis of a 1:1 complex between a designed monomeric interferon‐gamma and its soluble receptor

Randal

Kossiakoff

1998

Protein Science

View full text Add to dashboard Cite

Abstract:A variant of human interferon-gamma (IFN-y) has been created in which the two chains of the homodimeric cytokine were linked N-to C-terminus by an eight residue polypeptide linker. The sequence of this linker was derived from a loop in bira bifunctional protein, and was determined from a structural database search. This "single-chain" variant was used to create an IFN-y molecule that binds only a single copy of the a-chain receptor, rather than the 2 a-chain receptor: 1 IFN-y binding stoichiometry observed for the native hormone. Crystals have been grown of a 1 : 1 complex between this single-chain molecule and the extracellular domain of its a-chain receptor. These crystals diffract beyond 2.0 A, significantly better than the 2.9 8, observed for the native 2: 1 complex.Density calculations suggest these crystals contain two complexes in the asymmetric unit; a self-rotation function confirms this conclusion.Keywords: interferon-gamma; receptor; structure-based design; X-ray crystallography Interferon-y (IFN-y) is a homodimeric cytokine with potent antiviral, antiproliferative, and immunomodulatory activities (Wheelock, 1965;Farrar & Schreiber, 1993). It is expressed as a 143 amino acid polypeptide, with a post-translation modification resulting in a pyroglutamate amino terminus, the addition of carbohydrate, and a heterogeneous carboxyl terminus Rinderknecht et al., 1984;Pan et al., 1987). IFN-y exerts its various activities through receptor aggregation, a general mechanism common to the cytokine family (Sprang & Bazan, 1993). The first step of this process involves IFN-y binding to its high-affinity cell surface receptor, IFN-yRa, a member of the class-2 hematopoietic receptor superfamily (Schreiber & Celada, 1985;Langer & Pestka, 1988). While IFN-y has been shown to induce the dimerization of IFN-yRa (Greenlund et al., 1993) The ability to produce large quantities of fully active recombinant IFN-y (Gray et al., 1982; Tanaka et al., 1983) has made it the focus of numerous mutagenesis and structural studies aimed at establishing the determinants of receptor recognition. The X-ray crystal structure has been determined at 2.9 8, resolution of IFN-y with two copies of the extracellular domain of IFN-yRa bound symmetrically to the homodimer (Walter et al., 1995; S. Ealick, pers. comm.). This structure has provided details of the interaction between IFN-y and its high-affinity receptor, including the observation that the two receptors do not themselves interact. It also shows that the IFN-y residues in contact with the receptor form a discontinuous epitope made from residues on each monomer. One segment consists of helix A, the AB loop, and helix B from monomer one; the other consists of helix F and the C-terminus from the monomer two. Unfortunately, interpretation of structural detail is affected by the relatively limited resolution of this structure. In addition, this structure does not elucidate the role of the positively charged C-terminus of IFN-y, a segment shown by mutagenesis to be essential for re...

show abstract

A novel member of the interferon receptor family complements functionality of the murine interferon γ receptor in human cells

Cited by 199 publications

References 43 publications

The Jak–STAT pathway: specific signal transduction from the cell membrane to the nucleus

The Jak–STAT pathway: specific signal transduction from the cell membrane to the nucleus

The Stat1 Binding Motif of the Interferon-γ Receptor Is Sufficient to Mediate Stat5 Activation and Its Repression by SOCS3

Crystallization and preliminary X‐ray analysis of a 1:1 complex between a designed monomeric interferon‐gamma and its soluble receptor

Contact Info

Product

Resources

About