title: Characterization of a novel interaction between transcription factor TFII-I and the inducible tyrosine kinase in T cells.
abstract: TCR signaling leads to the activation of kinases such as inducible tyrosine kinase (Itk), a key regulatory protein in T-lymphocyte activation and function. The homolog of Itk in B cells is Bruton's tyrosine kinase, previously shown to bind and phosphorylate the transcription factor TFII-I. TFII-I plays major roles in transcription and signaling. Our purpose herein was twofold: first, to identify some of the molecular determinants involved in TFII-I activation downstream of receptor crosslinking in T cells and second, to uncover the existence of Itk-TFII-I signaling in T lymphocytes. We report for the first time that TFII-I is tyrosine phosphorylated upon TCR, TCR/CD43, and TCR/CD28 co-receptor engagement in human and/or murine T cells. We show that Itk physically interacts with TFII-I and potentiates TFII-I-driven c-fos transcription. We demonstrate that TFII-I is phosphorylated upon co-expression of WT, but not kinase-dead, or kinase-dead/R29C mutant Itk, suggesting these residues are important for TFII-I phosphorylation, presumably via an Itk-dependent mechanism. Structural analysis of TFII-I-Itk interactions revealed that the first 90 residues of TFII-I are dispensable for Itk binding. Mutations within Itk's kinase, pleckstrin-homology, and proline-rich regions did not abolish TFII-I-Itk binding. Our results provide an initial step in understanding the biological role of Itk-TFII-I signaling in T-cell function.
authors.affiliation: Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Mexico. catarina.sacristan@med.nyu.edu
authors.forename: Catarina
authors.initials: C
authors.lastname: Sacristán
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Schattgen
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Berg
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Bunnell
authors.forename: Ananda L
authors.initials: AL
authors.lastname: Roy
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Rosenstein
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D016762:Genes, fos / Q000235:genetics / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D051917:Leukosialin / Q000276:immunology / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019473:Transcription Factors, TFII / Q000378:metabolism*
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; C104259:GTF2I protein, human; D051917:Leukosialin; C465014:SPN protein, human; D019473:Transcription Factors, TFII; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase
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