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dc.contributor.authorYang, Wen-Chin
dc.contributor.authorChing, Keith A.
dc.contributor.authorTsoukas, Constantine D.
dc.contributor.authorBerg, Leslie J.
dc.date2022-08-11T08:09:31.000
dc.date.accessioned2022-08-23T16:34:06Z
dc.date.available2022-08-23T16:34:06Z
dc.date.issued2000-12-21
dc.date.submitted2009-03-10
dc.identifier.citation<p>J Immunol. 2001 Jan 1;166(1):387-95.</p>
dc.identifier.issn0022-1767 (Print)
dc.identifier.doi10.4049/jimmunol.166.1.387
dc.identifier.pmid11123316
dc.identifier.urihttp://hdl.handle.net/20.500.14038/38257
dc.description.abstractTec, the prototypical member of the Tec family of tyrosine kinases, is abundantly expressed in T cells and other hemopoietic cell types. Although the functions of Itk and Txk have recently been investigated, little is known about the role of Tec in T cells. Using antisense oligonucleotide treatment to deplete Tec protein from primary T cells, we demonstrate that Tec plays a role in TCR signaling leading to IL-2 gene induction. Interestingly, Tec kinases are the only known family of tyrosine kinases containing a pleckstrin homology (PH) domain. Using several PH domain mutants overexpressed in Jurkat T cells, we show that the Tec PH domain is required for Tec-mediated IL-2 gene induction and TCR-mediated Tec tyrosine phosphorylation. Furthermore, we show that Tec colocalizes with the TCR after TCR cross-linking, and that both the Tec PH and Src homology (SH) 2 domains play a role in this association. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, abolishes Tec-mediated IL-2 gene induction and Tec tyrosine phosphorylation, and partially suppresses Tec colocalization with the activated TCR. Thus, our data implicate the Tec kinase PH domain and phosphatidylinositol 3-kinase in Tec signaling downstream of the TCR.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=11123316&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.4049/jimmunol.166.1.387
dc.subject1-Phosphatidylinositol 3-Kinase
dc.subjectAmino Acid Substitution
dc.subjectAndrostadienes
dc.subjectAnimals
dc.subjectArginine
dc.subjectBlood Proteins
dc.subjectCysteine
dc.subjectEnzyme Inhibitors
dc.subjectGlutamic Acid
dc.subjectHumans
dc.subjectInterleukin-2
dc.subjectJurkat Cells
dc.subjectLysine
dc.subjectMice
dc.subjectMice, Transgenic
dc.subjectPhosphatidylinositol Phosphates
dc.subjectPhosphoproteins
dc.subjectPhosphorylation
dc.subjectPhosphotyrosine
dc.subjectProtein Binding
dc.subjectProtein Structure, Tertiary
dc.subjectProtein-Tyrosine Kinases
dc.subjectReceptor-CD3 Complex, Antigen, T-Cell
dc.subjectReceptors, Antigen, T-Cell
dc.subject*Sequence Homology, Amino Acid
dc.subjectSignal Transduction
dc.subjectT-Lymphocytes
dc.subjectTransfection
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleTec kinase signaling in T cells is regulated by phosphatidylinositol 3-kinase and the Tec pleckstrin homology domain
dc.typeJournal Article
dc.source.journaltitleJournal of immunology (Baltimore, Md. : 1950)
dc.source.volume166
dc.source.issue1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/1130
dc.identifier.contextkey770108
html.description.abstract<p>Tec, the prototypical member of the Tec family of tyrosine kinases, is abundantly expressed in T cells and other hemopoietic cell types. Although the functions of Itk and Txk have recently been investigated, little is known about the role of Tec in T cells. Using antisense oligonucleotide treatment to deplete Tec protein from primary T cells, we demonstrate that Tec plays a role in TCR signaling leading to IL-2 gene induction. Interestingly, Tec kinases are the only known family of tyrosine kinases containing a pleckstrin homology (PH) domain. Using several PH domain mutants overexpressed in Jurkat T cells, we show that the Tec PH domain is required for Tec-mediated IL-2 gene induction and TCR-mediated Tec tyrosine phosphorylation. Furthermore, we show that Tec colocalizes with the TCR after TCR cross-linking, and that both the Tec PH and Src homology (SH) 2 domains play a role in this association. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, abolishes Tec-mediated IL-2 gene induction and Tec tyrosine phosphorylation, and partially suppresses Tec colocalization with the activated TCR. Thus, our data implicate the Tec kinase PH domain and phosphatidylinositol 3-kinase in Tec signaling downstream of the TCR.</p>
dc.identifier.submissionpathoapubs/1130
dc.contributor.departmentDepartment of Pathology
dc.source.pages387-95


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