Multiple intracellular pathways induce expression of a zinc-finger encoding gene (EGR1): Relationship to activation of the Na/H exchanger
✍ Scribed by Dr. Gordon A. Jamieson Jr.; Ruth D. Mayforth Jr.; Mitchel L. Villereal; Vikas P. Sukhatme
- Publisher
- John Wiley and Sons
- Year
- 1989
- Tongue
- English
- Weight
- 832 KB
- Volume
- 139
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
inois 60637 lntracellular pathways that rapidly stimulate the expression of a mitogeninducible, zinc-finger encoding gene, EGRl (Sukhatme et al., Cell 53:37-431, have been characterized in two human fibroblasts strains (WI-38 and HSWP). Serum and epidermal growth factor (EGF) were each found to strongly stimulate EGRl expression in both cell types. Comparably high levels of expression could also be induced by treatment with the phorbol ester TPA. In cells rendered deficient in PK-C, serum and EGF were each still capable of inducing high levels of EGRl mRNA, demonstrating that additional non-protein kinase C pathways are capable of stimulating EGRl expression. In both fibroblasts strains, stimulation of EGRl expression by all these agents exhibited rapid, transient kinetics and could be superinduced if protein synthesis was inhibited through the addition of cycloheximide. Finally, various agents, known to stimulate/inhibit the activation of another early mitogenic response, the activation of Na/H exchange, were analyzed for their effect on EGRl expression. Interestingly bradykinin, vasopressin, and Ca ionophores, which dramatically stimulate Na/H exchange, were only weak stimulants of EGRl expression. Conversely, EGF, which stimulates Na/H exchange poorly, strongly activated EGRl expression. Hence while EGRl expression could be triggered by multiple intracellular pathways, its expression does not appear to require the prior activation of Na/H exchange.