Synergistic activation of the mkp-1 gene by protein kinase A signaling andUSF, but not c-Myc

Mitogen-activated protein kinase phosphatase 1 (MKP-1) is negatively regula ting mitogen-activated protein kinases and is therefore involved in early s ignaling processes. The expression of the mkp-1 gene is induced by growth f actors and stress. The promoters of the human and murine mkp-1 genes contai n several conserved DNA. binding elements, including two cAMP response elem ents and an E box. We observed that the upstream stimulatory factor (USF), but not c-Myc, activated mkp-1. USF synergized with protein kinase A, thus providing evidence for a role of the E box, during signal-regulated stimula tion of mkp-1. (C) 2000 Federation of European Biochemical Societies.