Pervanadate inhibits mitogen‐activated protein kinase kinase‐1 in a p38MAPK‐dependent manner

Abstract
In baboon smooth muscle cells (SMCs), pervanadate has a biphasic dose‐dependent effect on MEK‐1 activity. After a 30 min incubation period, low concentrations (1–10 μM) activate, while higher doses (30–100 μM) fail to stimulate MEK‐1. One possibility is that higher doses of pervanadate induce an additional signaling pathway that inhibits MEK‐1. Three lines of investigations provide support for the conclusion that this inhibitory effect is mediated by p38MAPK. First, pervanadate induces p38MAPK activity at concentrations that fail to activate MEK‐1. Second, pervanadate‐stimulated p38MAPK activity is maximal after a 10 min incubation, at a time, when MEK‐1 activity disappears. Third, addition of the specific p38MAPK inhibitor SB203580 preserves MEK‐1 activation by 100 μM pervanadate. The inhibitory effect of p38MAPK is probably not due to a phosphorylation of MEK‐1 although we can not rule out that other p38MAPK isoforms such as SAPK3 and SAPK4 may be involved, and may directly phosphorylate and inhibit MEK‐1.