Type I interferons (IFNs) are a family of cytokines that have antiviral and antiproliferative effects. Data regarding the processes by which these cytokines transduce signals from the cell membrane to the nucleus are becoming increasingly complex. The most characterized pathway is via JAK- STAT signaling. Previous studies established a potential role for the Src- family kinase Lck in JAK-STAT signaling. Therefore, this study was designed to analyze the role of Lck in IFN-α signaling by using the Jurkat, JCam (an Lck-defective cell line derived from Jurkat), and JCam/Lck (JCam cells with Lck restored). The results show that IFN-α can induce MAPK activity, but only in cells containing Lck. Furthermore, STATs1 and -3 are effectively phosphorylated and activated to bind DNA in the absence of Lck expression in IFN-α-treated cells. Finally, the results demonstrate that IFN-α exerts an antiproliferative effect in all three cell lines. These data indicate that Lck and active MAPK do not affect IFN-α-induced growth arrest or induction of STAT1s1 and -3 DNA binding ability.
Bibliographical noteFunding Information:
1This work was supported by U.S. Public Health Service Grants R01 CA 43264 and R01 CA 75895. 2To whom correspondence should be addressed at Department of Medical Microbiology and Immunology, University of South Florida, MDC 10, 12901 Bruce B. Downs Blvd., Tampa, FL 33612. Fax: 813-974-4151.
Copyright 2017 Elsevier B.V., All rights reserved.
- Molecular biology
- Signal transduction
- T lymphocytes