Human CD4/CD45RA+ and CD4/CD45RA T cell subsets express CD4-p56lck complexes, CD4-associated lipid kinases, TCR/CD3-p59fyn complexes, and share similar tyrosine kinase substrates |
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Authors: | Rothstein, David M. da Silva, Antonio Sugita, Kanji Yamamoto, Masahiro Prasad, K. V. S. Morimoto, Chikao Schiossman, Stuart F. Rudd, Christopher E. |
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Affiliation: | 1 Division of Tumor Immunology, Dana-Farber Cancer Institute 44 Binney Street Boston, MA 02115, USA 2 Division of Nephrology, Brigham and Women's Hospital Boston, MA 02115, USA 3 Department of Medicine, Harvard Medical School Boston, MA 02115, USA 4 Department of Pathology, Harvard Medical School Boston, MA 02115, USA |
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Abstract: | T cell activation appears to be regulated by an interplay betweenprotein tyrosine kinases (PTKs) and protein tyrosine phosphatases(PTPases). p56lck and p59fyn have been found to associate withCD4 and TCR-CD3 respectively. The CD45 family of transmembranePTPases has been shown to be able to regulate the activitiesof these receptor-associated PTKs in vitro. In man, CD45 containsfive different isoforms whose distribution defines subsets ofT cells having distinct activation requirements and in vitrofunctions.Several groups have reported a physical interaction betweendistinct isoforms of CD45 and CD2, CD4, and the TCR-CD3 complex.Given the potential regulatory interaction between CD45 andPTKs in CD4+ subsets expressing different CD45 isoforms, wehave examined CD4 associated and TCR-CD3– associated PTKactivities, associated phosphatidyl inositoi (PI) kinases andsubstrates of tyrosine phosphoryiation in CD45RA+and CD45RA–CD4+ T cell lines derived from peripheral blood. Both subsetsexpress CD4-assoclated p56lck and TCR-CD3-associated p59fynkinases which exhibit identical in vitro phosphoryiation atthe Y-394 and Y-420 autophosphorylation sites respectively.Further, both subsets exhibited PI kinases activity associatedwith CD4-p56lck. Consistent with these observations, anti-CD3crosslinklng induced the phosphoryiation of a similar spectrumof intracellular substrates in these CD45RA+and CD45RA–CD4+ T cell lines. These observations indicate that despitethe possible interaction between CD45 isoforms and CD4 or TCR-CD3,the mere expression of the CD45RA isoform does not in and ofitself alter the presence of receptorassociated kinases or theirintracellular targets. |
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Keywords: | T cell subsets tyrosine kinases tyrosine phosphatases |
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