High impact information on DUSP16

• This region of MKP7 interacts with beta-arrestin 2 at a central region near the JNK binding domain [1].
• These results indicate that activation of the ERK pathway strongly blocks JNK activation through stabilization of MKP-7 mediated by phosphorylation [2].
• We also determined that MKP-7 phosphorylated at Ser-446 has a longer half-life than unphosphorylated form of the wild type protein, as does a phospho-mimic mutant of MKP-7 [2].
• MKP7 then reassociates with beta-arrestin 2 on endocytic vesicles 30-60 min after initial receptor stimulation [1].
• By using U0126, a MEK inhibitor, and introducing several point mutations, we demonstrated that this upward mobility shift is because of phosphorylation and identified Ser-446 of MKP-7 as the phosphorylation site targeted by ERK activation [3].

Biological context of DUSP16

• Taken together, the functional data point to a context-dependent role for DUSP16 on cell transformation and apoptosis, reflecting the dual role of JNK, and therefore suggest that DUSP16 might be haploinsufficient for tumor suppression [4].
• Phosphorylation of Ser-446 determines stability of MKP-7 [2].
• In the present study, we have identified a novel MKP, designated MKP-7, and mapped it to human chromosome 12p12 [5].
• When expressed in mammalian cells MKP-7 protein was localized exclusively in the cytoplasm, but this localization became exclusively nuclear following leptomycin B treatment or introduction of a mutation in the nuclear export signal [5].

Anatomical context of DUSP16

• However, no inactivating mutations could be detected in leukemia patients hemizygous for DUSP16, and the effect of hemizygosity on DUSP16 expression level could not be assessed due to the variability of DUSP16 transcript levels observed in leukaemia cell lines and in patients [4].
• MKP-7 is predominantly localized in the cytoplasm when expressed in cultured cells, whereas hVH5 is both in the nucleus and the cytoplasm [6].
• In this study we found that, when expressed in COS-7 cells with HA-ERK2, the mobility of FLAG-MKP-7 was decreased on SDS-PAGE gels depending on several stimuli, including phorbol 12-myristate 13-acetate, fetal bovine serum, epidermal growth factor, H2O2, and ionomycin [3].

Associations of DUSP16 with chemical compounds

• These findings indicate that MKP-7 is the first identified leptomycin B-sensitive shuttle MKP [5].

Physical interactions of DUSP16

• MKP-7 binds to and inactivates p38 alpha and -beta, but not gamma or delta [6].

Other interactions of DUSP16

• A role for DUSP16 as a regulator of JNK signaling was further demonstrated via overexpression in Ba/F3 cells, which increased their antiapoptosis [4].

Analytical, diagnostic and therapeutic context of DUSP16

• Co-immunoprecipitation experiments and histological analysis suggested that MKP-7 determines the localization of MAPKs in the cytoplasm [5].

References