EXPRESSION OF V-SRC IN T-CELLS CORRELATES WITH NUCLEAR EXPRESSION OF NF-KAPPA-B

NF-kappa B is a rapidly inducible transcriptional activator that respo nds to a variety of signals and influences the expression of many gene s involved in the immune response. Protein tyrosine kinases transmit s ignals from cytokine and immune receptors. Very little information exi sts linking these two important classes of signaling molecules. We now demonstrate that v-scr expression correlates with nuclear expression of a kappa B binding complex similar to that induced by phorbol ester and ionomycin, as detected by electrophoretic mobility shift assay usi ng a variety of kappa B sites. This complex was blocked by the tyrosin e kinase inhibitor, herbimycin A. The v-src-induced complex comprised the p50 and p65 components of NF-kappa B, as determined by supershift and immunoblot analysis. As a functional correlate of this finding, tr ansient co-transfection of HIV-1 LTR reporter constructs in a differen t T cell line demonstrated that v-src activated this promoter in a kap pa B-dependent manner. We found that transactivation of the HIV-1 LTR by v-src was more sensitive to mutations of the proximal, rather that the distal, kappa B element. The implications for T cell receptor sign aling and HIV-1 gene expression are considered.