The gene for the human immune interferon receptor is located on chromosome 6.

Rashidbaigi, Abbas; Langer, Jerome A.; Jung, Vincent; Jones, Carol; Morse, Helvise G.; Tischfield, Jay A.; Trill, John J.; Kung, Hsiang‐Fu; Pestka, Sidney

doi:10.1073/pnas.83.2.384

Cited by 107 publications

(47 citation statements)

References 43 publications

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“…Thus, the antiproliferative pathway is intact in these cells but not fully activated via the human receptors. Similar results were also observed for different clones of mouse A9ϩ21 cells that carry several copies of human chromosome 21, which is thought to contain the type I IFN-R cluster (7,(11)(12)(13)(14)(15)(16)(41)(42)(43)(44)(45) and an uncharacterized signaling component (46,47). Altogether, these data indicate that (i) induction of the antiproliferative and antiviral responses occurs through partially divergent pathways and (ii) that a novel species-specific signaling component is required, in addition to the ␣ and ␤ L chains, for the growth inhibitory effect.…”

Section: Discussionsupporting

confidence: 66%

“…It has been reported that human/rodent somatic cell hybrids carrying human chromosome 21 acquire the ability to respond to the antiviral effect and induction of HLA class I antigens by human type I IFNs (7,(11)(12)(13)(14)(15)(16)(41)(42)(43)(44)(45). This is in part due to the fact that the ␣, ␤ S , and ␤ L subunits of the receptor are encoded by genes on this chromosome.…”

Section: Expression Of the Human ␣ And ␤ L Subunits Of The Type I Ifnmentioning

confidence: 97%

“…These data show that binding of growth inhibitory response. Since human/rodent somatic cell hybrids carrying human chromosome 21, including A9ϩ21 cells, have been shown to develop an antiviral state and induce HLA class I antigens in response to human type I IFNs (7,(11)(12)(13)(14)(15)(16)(41)(42)(43)(44)(45), the inability of these cells to respond to the antiproliferative effects of human type I IFNs further suggests that an additional species-specific signaling component is required. Moreover, it is unlikely that this signaling element is encoded by any genes present on human chromosome 21.…”

Section: Expression Of the Human ␣ And ␤ L Subunits Of The Type I Ifnmentioning

confidence: 99%

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Identification of a Domain in the β Subunit of the Type I Interferon (IFN) Receptor That Exhibits a Negative Regulatory Effect in the Growth Inhibitory Action of Type I IFNs

Platanias

Domanski

Nadeau

et al. 1998

Journal of Biological Chemistry

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Expression of human ␣ and long form of the ␤ (␤ L ) subunits of type I interferon receptor (IFN-R) in mouse cells is sufficient to activate the Jak-Stat pathway and to elicit an antiviral state in response to human IFN␣2 and IFN␤. We demonstrate herein, however, that these cells respond to the antiproliferative effects of murine IFN␣␤ but not human type I IFNs. These results suggest that an unknown species-specific component is required for the antiproliferative effect of human type I IFNs. The absence of this component can be complemented by expressing the human ␤ L chain truncated at amino acid 346. Thus, the distal region of ␤ L appears to function as a negative regulator of the growth inhibitory effects of type I IFNs. Further studies looking for possible targets of the ␤ L regulatory domain demonstrated that this region associates with a tyrosine phosphatase. These results suggest that a protein associated with the negative regulatory domain of ␤ L , likely a tyrosine phosphatase, plays a role in regulating the growth inhibitory effects of human type I IFNs.The most prominent effects of type I interferons (IFN) 1 are the antiviral and antiproliferative actions (1). These effects are mediated through binding to the type I interferon receptor (IFN-R or IFN␣R), which is composed of two subunits termed ␣, or IFNAR1, and ␤, or IFNAR2 (2-10). The genes encoding the different subunits of the type I IFN-R are clustered in the q22.1 region of human chromosome 21 (6,7,(11)(12)(13)(14)(15)(16)). This region also harbors an orphan class II cytokine receptor, the CRFB-4 gene, which is encoded on human chromosome 21 between the genes for the ␤ chain of the IFN␣R and the ␤ subunit of the IFN␥R (10, 17). Expression of the human ␣ and long form of the ␤ chain (␤ L ) subunits in mouse L-929 cells fully reconstitutes the activation of the Jak-Stat pathway and the induction of an antiviral state in response to HuIFN␣2 and HuIFN␤ (9). Furthermore, only the first 82 amino acids of the cytoplasmic domain of the ␤ L chain are required to activate the Jak-Stat pathway and induce the antiviral effect in response to IFN␣2 (18).The ␣ and ␤ subunits of the type I IFN-R associate with protein tyrosine kinases of the Jak family (4,8,18). The ␣ subunit interacts with Tyk2 (4,19,20) while the cytoplasmic domain of the ␤ L contains a docking site for Jak1 (18). Binding of type I IFNs to their receptor triggers rapid tyrosine phosphorylation of Tyk2 and Jak1 kinases, type I IFN-R subunits (21-25), and Stat factors (reviewed in Refs. 26 -28). Regulation of tyrosine kinase activity is mediated in most cytokine systems by protein tyrosine phosphatases (PTPs). For example, SHP1 (also named SHP, SHPTP1, HCP; PTP1C, Ref. 29), a predominantly hematopoietic tyrosine phosphatase that regulates the activity of the erythropoietin and IL-3 systems (30 -35), has also been implicated in IFN␣ signaling in hematopoietic cells (36,37). However, the role of SHP1 in other cell types is not clear since this PTP is mainly expressed in hematopoietic cells, wher...

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Section: Discussionsupporting

confidence: 66%

Section: Expression Of the Human ␣ And ␤ L Subunits Of The Type I Ifnmentioning

confidence: 97%

Section: Expression Of the Human ␣ And ␤ L Subunits Of The Type I Ifnmentioning

confidence: 99%

See 1 more Smart Citation

Identification of a Domain in the β Subunit of the Type I Interferon (IFN) Receptor That Exhibits a Negative Regulatory Effect in the Growth Inhibitory Action of Type I IFNs

Platanias

Domanski

Nadeau

et al. 1998

Journal of Biological Chemistry

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“…It is a 90-kd single-chain glycoprotein whose gene is encoded on chromosome 6. 27 For IFN-g's functional activity, an accessory molecule that is encoded on chromosome 21 is required to form a heterodimer. 28 All IFN receptors are species-specific.…”

Section: Interferonsmentioning

confidence: 99%

Actions of cytokines on the immune response and viral interactions: an overview

Peters¹

1996

Hepatology

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The central role of cytokines includes cell-to-cell com-the activity of leukocytes, or facilitate communication between different leukocytes. The molecule must also munication, inflammatory response amplification, and immune response regulation. This review will outline be characterized fully at the protein and DNA levels.Thus, all interleukins are cytokines, but some cytothe general actions of cytokines in inflammatory and immune responses and the mechanisms by which viral kines are not interleukins, because they are not products of leukocytes. Cytokines can either synergize or infections can evade these host defenses.Because of the multiple different systems in which antagonize other cytokines. These cytokine interactions lead to a cascade of functions. 4,5 Cytokines bind cytokines have been investigated, the nomenclature is confusing; the same cytokines have multiple names to specific receptors on the cell surface. Most cytokine receptors are two-chained polypeptides. 6 Cytokines can based on their biological response. Thus, the term cytokine has been designated to include mediators secreted mediate cell-to-cell communication which is separate from, or in addition to, contact-mediated cell-cell comby lymphocytes (lymphokines) and monocytes (monokines), as well as products of other cells involved in cell munication. The most important cytokines with respect to the liver are the IFNs, IL-1, IL-6, and tumor necrosis communication. Cytokines are generally small, single polypeptides approximately 20 kd in size and are char-factor (TNF). acterized by their transient production. 1,2 Their synthesis is transcriptionally regulated, with cytokine mes- CYTOKINE SIGNALINGsenger RNA (mRNA) generally being very short-lived.In recent years, there has been a veritable explosion Their structures are simple and their biological activi-of information about how cytokines signal their effects ties are characterized by pleiotropism, i.e., they have within cells. It was known that after cytokines bind to multiple different actions on a variety of cells, with a their receptors, they rapidly induce effects. However, redundancy of activities between cytokines. For exam-it was not known how this was accomplished. It is now ple, interleukin 6 (IL-6) was given diverse names, de-clear that there are common pathways for second-mespending on the assay in which it was discovered, in-senger signaling. These pathways, which were first decluding interferon (IFN)-b2, hepatocyte growth factor, scribed for interferon alfa (IFN-a), have been shown and plasma cell growth factor. While each name cor-for many other cytokines and are outlined below. rectly identified one action of IL-6, it did not suggest First, the cytokine binds to its receptor. Each cytothe wider functions we now ascribe to the interleukin. 3 kine receptor has a specific chain (usually named a The interleukin designation also has been introduced chain) which binds to the ligand; the other chain is to simplify confusing nomenclature. To be designated required for high-affinity bindin...

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“…The gene for the hIFN--yR is located on chromosome 6 (41,43). When this chromosome is present in human-murine somatic cell hybrids (29,41,43) or after transfection of the hIFN-yR gene into mouse cells (2), hIFN-,y binds with high affinity to the hIFN-yR but no biological response is elicited.…”

mentioning

confidence: 99%

The extracellular domain of the human interferon gamma receptor interacts with a species-specific signal transducer.

Gibbs¹,

Williams²,

Gray³

et al. 1991

Mol. Cell. Biol.

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At least two species-specific gene products are required for signal transduction by interferon gamma (IFN-y). The first is the IFN-y receptor, which binds ligand with high affinity in a species-specific manner. The second is an undetermined species-specific signal transducer(s). To determine whether the human IFN-y receptor (hIFN--yR) IFN-,y binds with high affinity (Kd = 10-9 to 10-11 M at 4°C) to a 90-kDa glycoprotein receptor present in low numbers (102 to 104) on a wide variety of cell types (7,16,19,33,36,42,51). Human and murine IFN-y share 40%o amino acid sequence identity (22) and exhibit species specificity with respect to receptor binding (15, 52) and biological activity (14,22). Human and murine IFN--y receptor (hIFN--yR and mIFN--yR, respectively) cDNAs have been cloned and expressed (2,12,23,25,32,39 affinity to the hIFN-yR but no biological response is elicited. The hIFN-yR as expressed in murine somatic cell hybrids and transfected mouse cells has binding properties similar to those of the hIFN--yR on human cells (1,7,36,42). These findings, in conjunction with results of cross-linking experiments (7,19,36,40), suggest that in contrast to the interleukin-6 (26, 54) and granulocyte-macrophage colony-stimulating factor receptors (21, 24), a second IFN--yR chain is not involved in mediating high-affinity ligand binding.Human-murine somatic cell hybrids containing human chromosomes 6 and 21 (29), as well as human-hamster and human-murine somatic cell hybrids containing human chromosome 21 and transfected with hIFN--yR expression vectors (17, 28), respond to hIFN-y as measured by the induction of MHC class I antigen. These findings demonstrate that the human chromosome 21-encoded factor(s) is necessary for signalling by the hIFN-yR, at least with respect to histocompatibility antigen expression, and suggest that the signal transducer(s) and the IFN-yR must be from the same species. How these two species-specific molecules function is unknown.To determine the region(s) of the IFN-yR that must be from the same species as the signal transducer to generate a functional response to IFN-y, we constructed expression vectors for human and hybrid human-murine IFN-y receptors. We transfected each expression vector into two different murine cell lines, one of which (SCC-16-5) contains a single copy of human chromosome 21. Transfectants were stimulated with hIFN-y and analyzed for increased expression of murine MHC class I antigen. Using this approach, we identified the region of the IFN--yR that cooperates with the species-specific signalling element(s).

show abstract

The gene for the human immune interferon receptor is located on chromosome 6.

Abstract: When 32P-labeled human recombinant immune interferon y (Hu-[32P]IFN-y) is crosslinked to human cells with disuccinimidyl suberateo a complex with a molecular

Cited by 107 publications

References 43 publications

Identification of a Domain in the β Subunit of the Type I Interferon (IFN) Receptor That Exhibits a Negative Regulatory Effect in the Growth Inhibitory Action of Type I IFNs

Identification of a Domain in the β Subunit of the Type I Interferon (IFN) Receptor That Exhibits a Negative Regulatory Effect in the Growth Inhibitory Action of Type I IFNs

Actions of cytokines on the immune response and viral interactions: an overview

The extracellular domain of the human interferon gamma receptor interacts with a species-specific signal transducer.

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