Characterization of a novel interaction between transcription factor TFII-I and the inducible tyrosine kinase in T cells

✍ Scribed by Catarina Sacristán; Stefan A. Schattgen; Leslie J. Berg; Stephen C. Bunnell; Ananda L. Roy; Yvonne Rosenstein

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 354 KB
• Volume: 39
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.200839031

✦ Synopsis

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.