Cooperation of ERK and SCFSkp2 for MKP-1 destruction provides a positive feedback regulation of proliferating signaling
YW Lin, JL Yang - Journal of Biological Chemistry, 2006 - ASBMB
The dual-specificity MAPK phosphatase MKP-1/CL100/DUSP1 is an inducible nuclear
protein controlled by p44/42 MAPK (ERK1/2) in a negative feedback mechanism to inhibit
kinase activity. Here, we report on the molecular basis for a novel positive feedback
mechanism to sustain ERK activation by triggering MKP-1 proteolysis. Active ERK2 docking
to the DEF motif (FXFP, residues 339–342) of N-terminally truncated MKP-1 in vitro initiated
phosphorylation at the Ser 296/Ser 323 domain, which was not affected by substituting Ala …
protein controlled by p44/42 MAPK (ERK1/2) in a negative feedback mechanism to inhibit
kinase activity. Here, we report on the molecular basis for a novel positive feedback
mechanism to sustain ERK activation by triggering MKP-1 proteolysis. Active ERK2 docking
to the DEF motif (FXFP, residues 339–342) of N-terminally truncated MKP-1 in vitro initiated
phosphorylation at the Ser 296/Ser 323 domain, which was not affected by substituting Ala …