Role of Txk, a Member of the Tec Family of Tyrosine Kinases, in Immune-Inflammatory Diseases

Abstract

Txk/Rlk, a member of the Tec family of tyrosine kinases, is an important signaling mediator. We previously reported that human Txk is expressed in Th1/Th0 cells, and Txk translocates from cytoplasm into nuclei upon activation. Txk regulates specifically interferon-γ gene transcription. Txk, poly(ADP-ribose) polymerase 1, and elongation factor 1α make a complex to bind to interferon-γ gene promoter region-53/-39 (Txk responsive element) to exert positive effects on transcription as a Th1 cell–associated transcription factor. Txk expression is enhanced in rheumatoid arthritis and Behçet's disease, where Th1 dominant immunity occurs. In bronchial asthma and atopic dermatitis, typical Th2 diseases, Txk expression is reduced. Modulation of Txk expression by gene transfer or similar modality may lead to the correction of aberrant immunity and, consequently, disease treatment.

Keywords:

• gene regulation
• human
• Th1/Th2
• T lymphocytes
• transcription factors