| http://purl.uniprot.org/citations/12093291 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12093291 | http://www.w3.org/2000/01/rdf-schema#comment | "The common cytokine receptor gamma chain (gamma c), an essential component of the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15, is critical for the development and function of lymphocytes. Recently, a novel lymphokine (IL-21) and its receptor (IL-21R alpha) were described which profoundly affect the growth and activation state of B, T, and NK cells in concert with other lymphokines or stimuli [Parrish-Novak, J., et al. (2000) Nature 408, 57-63]. In this report, we show that gamma c is also a required signaling component of the IL-21 receptor (IL-21R) using the gamma c-deficient X-linked severe combined immunodeficiency (XSCID) lymphoblastoid cell line JT, and JT cells reconstituted with gamma c (JT/gamma c). Moreover, we demonstrate a functional requirement for both gamma c and the gamma c-associated Janus family tyrosine kinase 3 (JAK3) in IL-21-induced proliferation of pro-B-lymphoid cells engineered to express human IL-21R alpha (BaF3/IL-21R alpha). Retroviral-mediated transduction of wild-type gamma c into XSCID JT cells restored function to the IL-21R, as shown by IL-21-induced tyrosine phosphorylation of JAK1 and JAK3, and downstream activation of STAT5, in JT/gamma c cells as well as BaF3/IL-21R alpha and primary splenic B cells. In contrast, IL-21 failed to activate the JAK-STAT pathway in nonreconstituted JT cells. Monoclonal antibodies specific for the gamma c chain effectively inhibited IL-21-induced growth of BaF3/IL-21R alpha cells, supporting a functional role for this molecule in the IL-21R complex. In addition, the specific JAK3 tyrosine kinase inhibitor WHI-P131 significantly reduced IL-21-induced proliferation of BaF3/IL-21R alpha cells. Taken together, these results definitively demonstrate that IL-21-mediated signaling requires the gamma c chain, and indicate that JAK3 is an essential transducer of gamma c-dependent survival and/or mitogenic signals induced by this cytokine."xsd:string |
| http://purl.uniprot.org/citations/12093291 | http://purl.org/dc/terms/identifier | "doi:10.1021/bi0202023"xsd:string |
| http://purl.uniprot.org/citations/12093291 | http://purl.uniprot.org/core/author | "Weinberg K."xsd:string |
| http://purl.uniprot.org/citations/12093291 | http://purl.uniprot.org/core/author | "Habib T."xsd:string |
| http://purl.uniprot.org/citations/12093291 | http://purl.uniprot.org/core/author | "Kaushansky K."xsd:string |
| http://purl.uniprot.org/citations/12093291 | http://purl.uniprot.org/core/author | "Senadheera S."xsd:string |
| http://purl.uniprot.org/citations/12093291 | http://purl.uniprot.org/core/date | "2002"xsd:gYear |
| http://purl.uniprot.org/citations/12093291 | http://purl.uniprot.org/core/name | "Biochemistry"xsd:string |
| http://purl.uniprot.org/citations/12093291 | http://purl.uniprot.org/core/pages | "8725-8731"xsd:string |
| http://purl.uniprot.org/citations/12093291 | http://purl.uniprot.org/core/title | "The common gamma chain (gamma c) is a required signaling component of the IL-21 receptor and supports IL-21-induced cell proliferation via JAK3."xsd:string |
| http://purl.uniprot.org/citations/12093291 | http://purl.uniprot.org/core/volume | "41"xsd:string |
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