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dc.contributor.authorFernandez, Belen
dc.contributor.authorCzech, Michael P.
dc.contributor.authorMeisner, Herman
dc.date2022-08-11T08:10:04.000
dc.date.accessioned2022-08-23T16:54:03Z
dc.date.available2022-08-23T16:54:03Z
dc.date.issued1999-07-10
dc.date.submitted2008-08-04
dc.identifier.citation<p>J Biol Chem. 1999 Jul 16;274(29):20244-50.</p>
dc.identifier.issn0021-9258 (Print)
dc.identifier.doi10.1074/jbc.274.29.20244
dc.identifier.pmid10400642
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42413
dc.description.abstractT lymphocyte activation through stimulation of the T cell receptor complex and co-stimulatory receptors is associated with acute tyrosine phosphorylation of intracellular proteins, which in turn mediate downstream signaling events that regulate interleukin-2 expression and cell proliferation. The extent of protein tyrosine phosphorylation is rapidly attenuated after only 1-2 min of stimulation as a means of tightly controlling the initial signaling response. Here we show that this attenuation of tyrosine phosphorylation of Shc, CrkL, and the proto-oncogene Cbl is mimicked by treatment of mouse T lymphocytes or cultured Jurkat cells with phorbol 12-myristate 13-acetate. This effect is blocked by the specific protein kinase C inhibitor GF109203X, but not by PD98059, an inhibitor of MEK1/2 kinase. Activation of protein kinase C by phorbol ester also causes rapid (t(1)/(2) = 2 min) dissociation of both CrkL and p85/phosphoinositide 3-kinase from Cbl concomitant with Cbl tyrosine dephosphorylation. More important, GF109203X treatment of Jurkat cells prior to T cell receptor stimulation by anti-CD3/CD4 antibodies results in an enhanced (2-fold) peak of Cbl phosphorylation compared with that observed in control cells. Furthermore, the rate of attenuation of both Cbl tyrosine phosphorylation and its association with CrkL following stimulation with anti-CD3/CD4 antibodies is much slower in Jurkat cells treated with GF109203X. Taken together, these data provide strong evidence that one or more isoforms of phorbol ester-responsive protein kinase C play a key role in a feedback mechanism that attenuates tyrosine phosphorylation of proteins and reverses formation of signaling complexes in response to T cell receptor activation.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=10400642&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1074/jbc.274.29.20244
dc.subject*Adaptor Proteins, Signal Transducing
dc.subject*Adaptor Proteins, Vesicular Transport
dc.subjectAnimals
dc.subjectHumans
dc.subjectJurkat Cells
dc.subjectLymphocyte Activation
dc.subjectMice
dc.subjectOncogene Protein v-cbl
dc.subjectProtein Kinase C
dc.subjectProtein Kinases
dc.subjectProteins
dc.subjectReceptors, Antigen, T-Cell
dc.subjectRetroviridae Proteins, Oncogenic
dc.subjectSignal Transduction
dc.subjectT-Lymphocytes
dc.subjectTetradecanoylphorbol Acetate
dc.subjectTyrosine
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleRole of protein kinase C in signal attenuation following T cell receptor engagement
dc.typeJournal Article
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume274
dc.source.issue29
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/765
dc.identifier.contextkey564680
html.description.abstract<p>T lymphocyte activation through stimulation of the T cell receptor complex and co-stimulatory receptors is associated with acute tyrosine phosphorylation of intracellular proteins, which in turn mediate downstream signaling events that regulate interleukin-2 expression and cell proliferation. The extent of protein tyrosine phosphorylation is rapidly attenuated after only 1-2 min of stimulation as a means of tightly controlling the initial signaling response. Here we show that this attenuation of tyrosine phosphorylation of Shc, CrkL, and the proto-oncogene Cbl is mimicked by treatment of mouse T lymphocytes or cultured Jurkat cells with phorbol 12-myristate 13-acetate. This effect is blocked by the specific protein kinase C inhibitor GF109203X, but not by PD98059, an inhibitor of MEK1/2 kinase. Activation of protein kinase C by phorbol ester also causes rapid (t(1)/(2) = 2 min) dissociation of both CrkL and p85/phosphoinositide 3-kinase from Cbl concomitant with Cbl tyrosine dephosphorylation. More important, GF109203X treatment of Jurkat cells prior to T cell receptor stimulation by anti-CD3/CD4 antibodies results in an enhanced (2-fold) peak of Cbl phosphorylation compared with that observed in control cells. Furthermore, the rate of attenuation of both Cbl tyrosine phosphorylation and its association with CrkL following stimulation with anti-CD3/CD4 antibodies is much slower in Jurkat cells treated with GF109203X. Taken together, these data provide strong evidence that one or more isoforms of phorbol ester-responsive protein kinase C play a key role in a feedback mechanism that attenuates tyrosine phosphorylation of proteins and reverses formation of signaling complexes in response to T cell receptor activation.</p>
dc.identifier.submissionpathoapubs/765
dc.contributor.departmentProgram in Molecular Medicine and the Department of Biochemistry and Molecular Biology
dc.source.pages20244-50


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