Protein tyrosine phosphorylation induced by ubiquitin-like polypeptide in murine T helper clone type 2.
Ubi-L, an isoform of the monoclonal nonspecific suppressor factor (MNSF), is an 8.5-kDa ubiquitin-like polypeptide. Ubi-L shows an antigen-nonspecific immunosuppressive action on various target cells including murine T helper type 2 clone, D10 cells. Most recently, we have characterized the biochemical nature of the receptor for Ubi-L. In this study, we observed that Ubi-L receptor ligation rapidly and transiently stimulated tyrosine phosphorylation of 65- and 31-kDa proteins in concanavalin A-activated D10 cells. The addition of neutralizing antibody to Ubi-L receptor inhibited the protein tyrosine phosphorylations and the Ubi-L-mediated suppression of IL-4 production by D10 cells. Genistein, a tyrosine kinase inhibitor, also reduced the induction of these protein tyrosine phosphorylations. IFNgamma, which is also known to inhibit the proliferative response of D10 cells, showed a synergistic effect with Ubi-L. Interestingly, IFNgamma enhanced the Ubi-L-induced tyrosine phosphorylation of the 31-kDa protein. These results suggest that tyrosine phosphorylation may be a key step in the initiation of the Ubi-L receptor-mediated transmembrane signaling.
Department of Biochemistry, Shimane Medical University, 89-1 Enya-cho, Izumo, 693-8501, Japan.
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Nakamura
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Tanigawa
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016227:Benzoquinones; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis; D047029:Lactams, Macrocyclic; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011506:Proteins / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction / Q000187:drug effects; D013491:Suppressor Factors, Immunologic / Q000378:metabolism* / Q000494:pharmacology; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D000906:Antibodies; D016227:Benzoquinones; D004791:Enzyme Inhibitors; D047029:Lactams, Macrocyclic; D020033:Protein Isoforms; D011506:Proteins; D011809:Quinones; D011956:Receptors, Cell Surface; D013491:Suppressor Factors, Immunologic; C119949:Ubi-L receptor; C072169:monoclonal nonspecific suppressor factor; D017828:Rifabutin; D015847:Interleukin-4; D014443:Tyrosine; C020754:herbimycin; D007371:Interferon-gamma; D019833:Genistein; D011505:Protein-Tyrosine Kinases