Construction and analysis of an EMBL‐3 phage library containing partially digested human chromosome 21‐specific DNA inserts (15–20 kb)

Janssen, Johannes W.G.; Collard, John G.; Tulp, A.; Cox, David; Millington-Ward, A. M.; Pearson, P. L.

doi:10.1002/cyto.990070504

Cited by 16 publications

(4 citation statements)

References 30 publications

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“…Cells and Cell Culture-SCC16 -5, a murine fibroblast cell line that contains a single copy of human chromosome 21 (33), and Colo-205, a human adenocarcinoma cell line, were cultured as described previously (26,34).…”

Section: Methodsmentioning

confidence: 99%

Identification of an Interferon-γ Receptor α Chain Sequence Required for JAK-1 Binding

Kaplan

Greenlund

Tanner

et al. 1996

Journal of Biological Chemistry

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We have shown previously that a four-amino acid block residing at positions 266-269 (LPKS) in the intracellular domain of the human interferon-gamma (IFN-gamma) receptor alpha chain is critical for IFN-gamma-dependent tyrosine kinase activation and biologic response induction. Herein we show that this sequence is required for the constitutive attachment of the tyrosine kinase JAK-1. Using a vaccinia expression system, a receptor alpha chain-specific monoclonal antibody coprecipitated JAK-1 from cells coexpressing JAK-1 and either (a) wild type IFN-gamma receptor alpha chain, (b) a receptor alpha chain truncation mutant containing only the first 59 intracellular domain amino acids, or (c) a receptor mutant containing alanine substitutions for the functionally irrelevant residues 272-275. In contrast, JAK-1 was not coprecipitated when coexpressed with a receptor alpha chain mutant containing alanine substitutions for the functionally critical residues 266-269 (LPKS). Mutagenesis of the LPKS sequence revealed that Pro-267 is the only residue obligatorily required for receptor function. In addition, Pro-267 is required for JAK-1 binding. These results thus identify a site in the IFN-gamma receptor alpha chain required for constitutive JAK-1 association and establish that this association is critical for IFN-gamma signal transduction.

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Section: Methodsmentioning

confidence: 99%

Identification of an Interferon-γ Receptor α Chain Sequence Required for JAK-1 Binding

Kaplan

Greenlund

Tanner

et al. 1996

Journal of Biological Chemistry

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“…The murine cell line SCC-16-5 (SCC; provided by R. Schreiber, Washington University, St. Louis, Mo.) is a human-murine L-cell somatic cell hybrid which contains a single copy of human chromosome 21 (27). It was grown in Dulbecco's modified Eagle medium with 10% fetal calf serum, 2 mM L-glutamine, 50 U of penicillin per ml, and 50 ,ug of streptomycin per ml.…”

Section: Methodsmentioning

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).

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“…2 It is interesting that the requirement for the corresponding tyrosine residue of human IFNGR1, Tyr 440 , appears to be different: in primary human fibroblasts lacking IFNGR1 and reconstituted with the Y440F mutant, the expression of ISGs in response to IFN␥ was substantial, although the antiviral effect was inhibited. 3 The hybrid murine fibroblast cell line SCC16-5, containing a single copy of human chromosome 21 encoding human IFNGR2, was used initially to characterize human IF-NGR1 (49,50). The expression of various mutants of IFNGR1 in these cells revealed that Tyr 440 is required for STAT1 activation and antiviral activity (29,51).…”

Section: Contribution Of Specific Tyrosinementioning

confidence: 99%

Role of Tyrosine 441 of Interferon-γ Receptor Subunit 1 in SOCS-1-mediated Attenuation of STAT1 Activation

Qing

Costa-Pereira

Watling

et al. 2005

Journal of Biological Chemistry

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Suppressor of cytokine signaling (SOCS)-1, the key negative regulator of interferon (IFN)-␥-dependent signaling, is induced in response to IFN␥. SOCS-1 binds to and inhibits the IFN␥ receptor-associated kinase Janusactivated kinase (JAK) 2 and inhibits its function in vitro, but the mechanism by which SOCS-1 inhibits IFN␥-dependent signaling in vivo is not clear. Upon stimulation, mouse IFN␥ receptor subunit 1 (IFNGR1) is phosphorylated on several cytoplasmic tyrosine residues, and Tyr 419 is required for signal transducer and activator of transcription (STAT) 1 activation in mouse embryo fibroblasts. However, the functions of the other three cytoplasmic tyrosine residues are not known. Here we show that Tyr 441 is required to attenuate STAT1 activation in response to IFN␥. Several tyrosine to phenylalanine mutants of IFNGR1, expressed at normal levels in stable pools of IFNGR1-null cells, were analyzed for the phosphorylation of STAT1 during a 48-h period, and antiviral activity in response to IFN␥ was also measured. Stronger activation of STAT1 was observed in cells expressing all IFNGR1 variants mutated at Tyr 441 , and, consistently, stronger antiviral activity was also observed in these cells. Interferon (IFN)1 -␥ plays key roles in mediating antiviral and antigrowth responses and in modulating immune responses (1). The major signal transduction pathway activated by IFN␥ has been elucidated through both biochemical and genetic studies. The IFN␥ receptor complex consists of two receptor subunits, IFNGR1 and IFNGR2, and the tyrosine kinases Janus-activated kinase (JAK) 1 and JAK2, which bind to IFNGR1 and IFNGR2, respectively. IFN␥ induces the oligomerization of the receptor subunits, leading to the activation of JAK1 and JAK2, which then phosphorylate tyrosine residues within the cytoplasmic domain of IFNGR1. Signal transducer and activator of transcription (STAT) 1 is then recruited to the receptor complex and phosphorylated on Tyr 701 , allowing it to be released, form homodimers, translocate to the nucleus, and bind to ␥-activated sequences to activate the transcription of interferon-stimulated genes (ISGs) (1-3).The activation of STAT1 by IFN␥ is tightly controlled by several mechanisms (4). The SH2-containing phosphatase 2 binds to IFNGR1 and inhibits STAT1 activation without inhibiting the phosphorylation of IFNGR1 (5). Protein inhibitor of activated STAT 1 (PIAS-1) binds to STAT1 and prevents its association with target DNA (6). Both genetic and biochemical studies have shown that suppressor of cytokine signaling (SOCS)-1 is the most potent inhibitor of IFN␥ signaling (7). Mice lacking SOCS-1 develop a complex fatal neonatal disease (8 -10), and the mortality, which results from hypersensitivity to IFN␥, is largely prevented by administration of anti-IFN␥. In addition, premature death does not occur in mice lacking both 11). In response to IFN␥, STAT1 activation is much stronger in cells lacking SOCS-1 than in wild-type cells (11,12). The constitutive expression of SOCS-1 blocks IFN␥-mediated antivir...

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Construction and analysis of an EMBL‐3 phage library containing partially digested human chromosome 21‐specific DNA inserts (15–20 kb)

Cited by 16 publications

References 30 publications

Identification of an Interferon-γ Receptor α Chain Sequence Required for JAK-1 Binding

Identification of an Interferon-γ Receptor α Chain Sequence Required for JAK-1 Binding

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

Role of Tyrosine 441 of Interferon-γ Receptor Subunit 1 in SOCS-1-mediated Attenuation of STAT1 Activation

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