Phosphatase Subfamily DSP10

Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily DSP10 (MKP5)

DSP10 selectively dephosphorylates p38 and JNK. It is conserved across holozoan but lost in nematodes.

Evolution

DSP10 (MKP5) subfamily is found in most holozoan except nematodes. DSP10 is usually one copy per genome, e.g. DUSP10 in human.

Domain

DSP10 has two domains: rhodanese domain and phosphatase domain. Rhodanese domain can bind to kinases [1].

Function

DUSP10 is phosphatase specific for p38 and SAPK/JNK. It binds to p38 and SAPK/JNK, but not to MAPK/ERK, and inactivates p38 and SAPK/JNK, but not MAPK/ERK. p38 is a preferred substrate. It is present evenly in both the cytoplasm and the nucleus. DUSP10 is widely expressed in various tissues and organs, and its expression in cultured cells is elevated by stress stimuli [2, 3, 4].

On the other hand, it has been reported that DUSP10 interacts with ERK, retains it in the cytoplasm, suppresses its activation and downregulates ERK-dependent transcription [5].

Human DUSP10 is frequently upregulated in colorectal cancer (CRC). Certain mutations in DUSP10 correlate with the incidence of CRC. DUSP10/MKP5 also negatively regulates intestinal epithelial cell growth [6].

References

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