Compositions and methods are provided for potentiating the activity of the
mitogen-activated protein kinase p38. In particular the mitogen-activated
protein kinase kinase MEK6, and variants thereof that stimulate
phosphorylation of p38 are provided. Such compounds may be used, for
example, for therapy of diseases associated with the p38 cascade and to
identify antibodies and other agents that inhibit or activate signal
transduction via p38.