A novel site on dual-specificity phosphatase MKP7/DUSP16 is required for catalysis and MAPK binding.

ABSTRACT: The dual-specificity phosphatases responsible for the inactivation of the mitogen-activated protein kinases (MAPKs) are designated as the MAPK phosphatases (MKPs). We demonstrated previously that MKP5 is regulated through a novel allosteric site suggesting additional regulatory mechanisms of catalysis exist amongst the MKPs. Here, we sought to determine whether the equivalent site within the phosphatase domain of a highly similar MKP family member, MKP7, is also important for phosphatase function. We found that mutation of tyrosine 271 (Y271) in MKP7, which represents the comparable Y435 within the MKP5 allosteric pocket, inhibited MKP7 catalytic activity. Consistent with this, when MKP7 Y271 mutants were overexpressed in cells, the substrates of MKP7, p38 MAPK or JNK, failed to undergo de

SUBMITTER: Shillingford S 

PROVIDER: S-EPMC9676401 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature