| Intriguingly , active ERK promoted phospho Ser ( 296 ) MKP 1 bound to SCF ( Skp 2 ) ubiquitin ligase in vivo and in vitro . ^^^ Forced expression of Skp 2 enhanced MKP 1 polyubiquitination and proteolysis upon ERK activation , whereas depletion of endogenous Skp 2 suppressed such events . ^^^ The kinetics of ERK signaling stimulated by serum correlated with the endogenous MKP 1 degradation rate in a Skp 2 dependent manner . ^^^ Thus , MKP 1 proteolysis can be achieved via ERK and SCF ( Skp 2 ) cooperation , thereby sustaining ERK activation . . ^^^ |