TY - JOUR
T1 - Induction of interleukin‐2 transcription by the hamster polyomavirus middle T antigen
T2 - a role for Fyn in T cell signal transduction
AU - Brizuela, Leonardo
AU - Ulug, Emin T.
AU - Jones, Margaret A.
AU - Courtneidge, Sara A.
PY - 1995/2
Y1 - 1995/2
N2 - 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 NFxB reporter constructs. The immunosuppressant FK506 as well as dominant negative alleles of Ras 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.
AB - 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 NFxB reporter constructs. The immunosuppressant FK506 as well as dominant negative alleles of Ras 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.
KW - Fyn
KW - Interleukin‐2 transcription
KW - Phosphalipase Cγ
KW - Polyomavirus middle T antigen
KW - Src
UR - http://www.scopus.com/inward/record.url?scp=0028953833&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028953833&partnerID=8YFLogxK
U2 - 10.1002/eji.1830250212
DO - 10.1002/eji.1830250212
M3 - Article
C2 - 7875200
AN - SCOPUS:0028953833
SN - 0014-2980
VL - 25
SP - 385
EP - 393
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 2
ER -