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 responds to a variety of signals and influences the expression of many genes involved in the immune response. Protein tyrosine kinases transmit signals from cytokine and immune receptors. Very little information exists linking these two important classes of signaling molecules. We now demonstrate that v-src 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 using a variety of kappa B sites. This complex was blocked by the tyrosine 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, transient co-transfection of HIV-1 LTR reporter constructs in a different T cell line demonstrated that v-src activated this promoter in a kappa B-dependent manner. We found that transactivation of the HIV-1 LTR by v-src was more sensitive to mutations of the proximal, rather than the distal, kappa B element. The implications for T cell receptor signaling and HIV-1 gene expression are considered.
Eicher
D M
DM
Leukocyte Cell Biology Section, NCI-FCRDC, Frederick, MD 21702-1201.
Tan
T H
TH
Rice
N R
NR
O'Shea
J J
JJ
Kennedy
I C
IC
D001483:Base Sequence; D002467:Cell Nucleus / Q000737:chemistry*; D015870:Gene Expression; D016391:Genes, src; D016325:HIV Long Terminal Repeat; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000032:analysis*; D013601:T-Lymphocytes / Q000737:chemistry*; D015533:Transcriptional Activation
D016328:NF-kappa B