CD45 modulates T cell receptor/CD3-induced activation of human thymocytes via regulation of tyrosine phosphorylation
dc.contributor.author | Turka, Laurence A. | en_US |
dc.contributor.author | Kanner, Steven B. | en_US |
dc.contributor.author | Schieven, Gary L. | en_US |
dc.contributor.author | Thompson, Craig B. | en_US |
dc.contributor.author | Ledbetter, Jeffrey A. | en_US |
dc.date.accessioned | 2006-04-28T16:33:09Z | |
dc.date.available | 2006-04-28T16:33:09Z | |
dc.date.issued | 1992-02 | en_US |
dc.identifier.citation | Turka, Laurence A.; Kanner, Steven B.; Schieven, Gary L.; Thompson, Craig B.; Ledbetter, Jeffrey A. (1992)."CD45 modulates T cell receptor/CD3-induced activation of human thymocytes via regulation of tyrosine phosphorylation." European Journal of Immunology 22(2): 551-557. <http://hdl.handle.net/2027.42/37960> | en_US |
dc.identifier.issn | 0014-2980 | en_US |
dc.identifier.issn | 1521-4141 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/37960 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=1371471&dopt=citation | en_US |
dc.description.abstract | Stimulation of thymocytes or mature T cells via the T cell receptor (TcR)/CD3 complex activates a cascade of processes inducing cells to enter the cell cycle. A key step is the activation of phosphatidylinositol-specific phospholipase C (PI-PLC) within seconds following TcR/CD3 stimulation, an event which is strongly enhanced by co-ligation of the CD4 (or CD8) accessory molecule with TcR/CD3. In contrast, co-ligation of CD45 inhibits the same TcR/CD3 responses. The machinery which couples the TcR/CD3 complex, CD4, and CD45 to PI-PLC appears to involve regulation of tyrosine phosphorylation, as the TcR/CD3 and CD4 receptors are associated with the tyrosine kinases p59 fyn and p56 lck , respectively, and CD45 has intrinsic tyrosine phosphatase activity. Here, we have examined the ability of CD45 to regulate signal transduction via TcR/CD3 in human thymocytes. Co-cross-linking CD45 to the TcR/CD3 complex strongly suppressed the tyrosine phosphorylation of several intracellular substrates normally seen following TcR/CD3 stimulation. This effect of CD45 was associated with inhibition of a rise in intracellular calcium following TcR/CD3 ligation. Since TcR/CD3 stimulation of mature T cells induces tyrosine phosphorylation of PLC Γ 1, we investigated this phenomenon in thymocytes, and asked whether ligation of CD45 might regulate this process. By immunoprecipitation we found that TcR/CD3 stimulation induced tyrosine phosphorylation of PLC Γ 1, an effect which was enhanced by co-cross-linking CD4 to TcR/CD3. In contrast, co-ligation of CD45 strongly blocked PLC Γ 1 phosphorylation induced by either stimulus. Consistent with previous findings in mature T cells, CD45 cross-linking was able to partially inhibit TcR/CD3-induced thymocyte proliferation when interleukin 2 was used as a second signal, but almost completely (80%–90%) blocked proliferation when anti-CD28 mAb was used as the second signal, suggesting that CD45 cross-linking may be able to block interleukin 2 production via the CD28 pathway. These effects of CD45 on TcR/CD3 signaling and proliferation in thymocytes point towards a potential role for this pathway in thymic selection. | en_US |
dc.format.extent | 891944 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | WILEY-VCH Verlag GmbH | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Microbiology and Immunology | en_US |
dc.title | CD45 modulates T cell receptor/CD3-induced activation of human thymocytes via regulation of tyrosine phosphorylation | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Biological Chemistry | en_US |
dc.subject.hlbsecondlevel | Public Health | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Medicine, University of Michigan, Ann Arbor, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle ; University of Michigan, MSRB-II, Room 1560, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA | en_US |
dc.contributor.affiliationum | Department of Microbiology/Immunology, University of Michigan, Ann Arbor, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle | en_US |
dc.contributor.affiliationum | Department of Microbiology/Immunology, University of Michigan, Ann Arbor, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle | en_US |
dc.contributor.affiliationum | Department of Medicine, University of Michigan, Ann Arbor, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle ; Department of Microbiology/Immunology, University of Michigan, Ann Arbor, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle ; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle | en_US |
dc.contributor.affiliationum | Department of Microbiology/Immunology, University of Michigan, Ann Arbor, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle ; Department of Microbiology, University of Washington, Seattle | en_US |
dc.identifier.pmid | 1371471 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/37960/1/1830220238_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/(ISSN)1521-4141 | en_US |
dc.identifier.source | European Journal of Immunology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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