Identification of Residues of the IFNAR1 Chain of the Type I Human Interferon Receptor Critical for Ligand Binding and Biological Activity†

Biochemistry ◽  
2004 ◽  
Vol 43 (39) ◽  
pp. 12498-12512 ◽  
Author(s):  
Chantal Cajean-Feroldi ◽  
Florence Nosal ◽  
Pierre C. Nardeux ◽  
Xavier Gallet ◽  
Jacqueline Guymarho ◽  
...  
Keyword(s):  
Biological Activity ◽  
Ligand Binding ◽  
Human Interferon ◽  
Type I ◽  
Interferon Receptor

scholarly journals Contributions of cloned type I interferon receptor subunits to differential ligand binding 1

FEBS Letters ◽  
1997 ◽  
Vol 404 (2-3) ◽  
pp. 197-202 ◽  
Author(s):  
Elizabeth Cali Cutrone ◽  
Jerome A Langer
Keyword(s):  
Ligand Binding ◽  
Type I Interferon ◽  
Type I ◽  
Interferon Receptor

scholarly journals Ligand-induced association of the type I interferon receptor components.

1995 ◽  
Vol 15 (8) ◽  
pp. 4208-4214 ◽  
Author(s):  
B Cohen ◽  
D Novick ◽  
S Barak ◽  
M Rubinstein
Keyword(s):  
Ligand Binding ◽  
Type I Interferon ◽  
Common Type ◽  
Host Cells ◽  
Type I ◽  
High Affinity ◽  
Ifn Alpha ◽  
Essential Components ◽  
Interferon Receptor ◽  
Alpha Beta

Two transmembrane polypeptides, IFNAR and IFN-alpha/Beta R, were previously identified as essential components of the type I interferon (IFN) receptor, but their interrelationship and role in ligand binding were not clear. To study these issues, we stably expressed and characterized the two polypeptides in host murine cells. In human cells, native IFN-alpha/beta R is a 102-kDa protein but upon reduction only a 51-kDa protein is detected. In host murine cells human IFN-alpha/beta R was expressed as a 51-kDa protein. Host cells expressing IFN-alpha/beta R bound IFN-alpha 2 with a high affinity (Kd of 3.6 nM), whereas cells expressing IFNAR exhibited no ligand binding. Upon coexpression of IFNAR and the 51-kDa IFN-alpha/beta R, the affinity for IFN-alpha 2 was increased 10-fold, approaching that of the native receptor. We show by cross-linking that both the cloned (51-kDa) and native (102-kDa) IFN-alpha/beta R bind IFN-alpha 2 to form an intermediate product, while IFNAR associates with this product to form a ternary complex. Hence, IFNAR and IFN-alpha/beta R are components of a common type I IFN receptor, cooperating in ligand binding. Ligand-induced association of IFNAR and IFN-alpha/beta R probably triggers transmembrane signaling.

scholarly journals Ligand-independent interaction of the type I interferon receptor complex is necessary to observe its biological activity

Cytokine ◽  
2013 ◽  
Vol 64 (1) ◽  
pp. 286-297 ◽  
Author(s):  
Christopher D. Krause ◽  
Gina Digioia ◽  
Lara S. Izotova ◽  
Junxia Xie ◽  
Youngsun Kim ◽  
...  
Keyword(s):  
Biological Activity ◽  
Type I Interferon ◽  
Type I ◽  
Receptor Complex ◽  
Interferon Receptor

scholarly journals Determination of the human type I interferon receptor binding site on human interferon-α2 by cross saturation and an NMR-based model of the complex

2006 ◽  
Vol 15 (11) ◽  
pp. 2656-2668 ◽  
Author(s):  
Sabine R. Quadt-Akabayov ◽  
Jordan H. Chill ◽  
Rina Levy ◽  
Naama Kessler ◽  
Jacob Anglister
Keyword(s):  
Binding Site ◽  
Receptor Binding ◽  
Type I Interferon ◽  
Human Interferon ◽  
Type I ◽  
Receptor Binding Site ◽  
Human Type ◽  
Interferon Receptor ◽  
Interferon Α2

Mapping Human Interferon-alpha (IFN-α2) Binding Determinants of the Type I Interferon Receptor Subunit IFNAR-1 with Human/Bovine IFNAR-1 Chimeras

Biochemistry ◽  
1998 ◽  
Vol 37 (37) ◽  
pp. 13003-13010 ◽  
Author(s):  
Lisa A. Goldman ◽  
Elizabeth Cali Cutrone ◽  
Anju Dang ◽  
Xiaoming Hao ◽  
Jin-kyu Lim ◽  
...  
Keyword(s):  
Interferon Alpha ◽  
Type I Interferon ◽  
Human Interferon ◽  
Type I ◽  
Receptor Subunit ◽  
Interferon Receptor ◽  
Binding Determinants

scholarly journals Mechanisms of Transforming Growth Factor-β Receptor Endocytosis and Intracellular Sorting Differ between Fibroblasts and Epithelial Cells

2001 ◽  
Vol 12 (3) ◽  
pp. 675-684 ◽  
Author(s):  
Jules J.E. Doré ◽  
Diying Yao ◽  
Maryanne Edens ◽  
Nandor Garamszegi ◽  
Elizabeth L. Sholl ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Ligand Binding ◽  
Transforming Growth Factor ◽  
Point Mutations ◽  
Type I ◽  
Receptor Complex ◽  
Type Ii ◽  
Down Regulation ◽  
Β Receptor

Transforming growth factor-βs (TGF-β) are multifunctional proteins capable of either stimulating or inhibiting mitosis, depending on the cell type. These diverse cellular responses are caused by stimulating a single receptor complex composed of type I and type II receptors. Using a chimeric receptor model where the granulocyte/monocyte colony-stimulating factor receptor ligand binding domains are fused to the transmembrane and cytoplasmic signaling domains of the TGF-β type I and II receptors, we wished to describe the role(s) of specific amino acid residues in regulating ligand-mediated endocytosis and signaling in fibroblasts and epithelial cells. Specific point mutations were introduced at Y182, T200, and Y249 of the type I receptor and K277 and P525 of the type II receptor. Mutation of either Y182 or Y249, residues within two putative consensus tyrosine-based internalization motifs, had no effect on endocytosis or signaling. This is in contrast to mutation of T200 to valine, which resulted in ablation of signaling in both cell types, while only abolishing receptor down-regulation in fibroblasts. Moreover, in the absence of ligand, both fibroblasts and epithelial cells constitutively internalize and recycle the TGF-β receptor complex back to the plasma membrane. The data indicate fundamental differences between mesenchymal and epithelial cells in endocytic sorting and suggest that ligand binding diverts heteromeric receptors from the default recycling pool to a pathway mediating receptor down-regulation and signaling.

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