Characterization of an ERK-binding domain in microphthalmia-associated transcription factor and differential inhibition of ERK2-mediated substrate phosphorylation.

ABSTRACT: Efficient and specific signaling by mitogen-activated protein kinases (MAPKs) is enhanced by docking sites found on many MAPK substrates and regulators. Here we show that the MAPKs ERK1 and ERK2 form a stable complex (Kd approximately 6 microm) with their substrate the microphthalmia-associated transcription factor (MITF). Complex formation requires a domain of MITF of approximately 100 residues that is nearby, but C-terminal to, the MAPK phosphorylation site at Ser73. MITF derivatives lacking this ERK-binding domain do not bind ERK2 and are phosphorylated less efficiently by ERK2. The ERK-binding domain of MITF bears no obvious resemblance to previously characterized MAPK docking motifs; in particular, it does not contain a consensus D-site. Consistent with this, ERK2-MITF binding does no

SUBMITTER: Molina DM 

PROVIDER: S-EPMC3017498 | biostudies-literature | 2005 Dec

REPOSITORIES: biostudies-literature