Induction of interleukin-2 transcription by the hamster polyomavirus middle T antigen

A role for Fyn in T cell signal transduction

Leonardo Brizuela, Emin T. Ulug, Margaret A. Jones, Sara Courtneidge

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The transforming protein of mouse polyomavirus, the mouse middle T antigen (MomT), and its counterpart in the hamster polyomavirus, the hamster middle T antigen (HamT), interact with a number of cellular proteins. Among these are members of the Src family of tyrosine kinases, the phosphatidylinositol 3-kinase, the serine/threonine phosphatase PP2A and the adaptor protein Shc (in the case of MomT). However, both the relative affinity of these antigens for the members of the Src family and the tumor profile induced by their respective viruses are quite distinct. Particularly noteworthy are the preferential binding of Fyn by HamT and the induction of lymphoid malignancies by the hamster polyomavirus. Here we report that, when expressed in fibroblasts, HamT also associated with phospholipase Cγ (PLCγ), which led to an increased intracellular concentration of inositol-1, 4, 5-trisphosphate. We also show that expression of HamT in the mouse T cell line EL4 was sufficient to induce transcription from interleukin-2 (IL-2), NFAT and NFκB reporter constructs. The immunosuppressant FK506 as well as dominant negative alleles of Pas and Raf inhibited HamT-induced IL-2 transcription. This, together with the observation of NFAT responses, suggests that the action of HamT depended at least in part on the integrity of signal transduction pathways elicited by activated PLCγ. Furthermore, dominant negative Fyn but not the equivalent allele of Lck blocked HamT activation of IL-2 transcription, while both Lck and Fyn dominant negative alleles blocked LT cell receptor-mediated IL-2 transcriptional activation. These results support the hypothesis that Fyn is involved in signal transduction events leading to IL-2 transcriptional activation in T cells. Finally, the activation of IL-2 transcription by HamT and not by MomT shown here parallels the ability of the hamster polyomavirus to induce lymphoid malignancies.

Original languageEnglish (US)
Pages (from-to)385-393
Number of pages9
JournalEuropean Journal of Immunology
Volume25
Issue number2
DOIs
StatePublished - Feb 1995
Externally publishedYes

Fingerprint

Polyomavirus Transforming Antigens
Polyomavirus
Viral Tumor Antigens
Interleukin-2
Cricetinae
Signal Transduction
T-Lymphocytes
Alleles
Type C Phospholipases
Transcriptional Activation
Shc Signaling Adaptor Proteins
Phosphatidylinositol 3-Kinase
Neoplasms
Aptitude
Inositol 1,4,5-Trisphosphate
src-Family Kinases
Interleukin-2 Receptors
Phosphoprotein Phosphatases
Tacrolimus
Immunosuppressive Agents

Keywords

  • Fyn
  • Interleukin-2 transcription
  • Phosphalipase Cγ
  • Polyomavirus middle T antigen
  • Src

ASJC Scopus subject areas

  • Immunology

Cite this

Induction of interleukin-2 transcription by the hamster polyomavirus middle T antigen : A role for Fyn in T cell signal transduction. / Brizuela, Leonardo; Ulug, Emin T.; Jones, Margaret A.; Courtneidge, Sara.

In: European Journal of Immunology, Vol. 25, No. 2, 02.1995, p. 385-393.

Research output: Contribution to journalArticle

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