Characterization of a novel interaction between transcription factor TFII-I and the inducible tyrosine kinase in T cells.
Department of Pathology
Life Sciences | Medicine and Health Sciences
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.
DOI of Published Version
Eur J Immunol. 2009 Aug 21;39(9):2584-2595. Link to article on publisher's website
European Journal of Immunology
Sacristan C, Schattgen SA, Berg LJ, Bunnell SC, Roy AL, Rosenstein Y. (2009). Characterization of a novel interaction between transcription factor TFII-I and the inducible tyrosine kinase in T cells.. GSBS Student Publications. https://doi.org/10.1002/eji.200839031. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1629