Phosphatase Subfamily DSP10

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

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

Evolution

The DSP10 (MKP5) subfamily is found in most holozoa. DSP10 is usually one copy per genome, e.g. DUSP10 (MKP5) in human. DSP10 is lost from nematodes, and dipteran insects have lost the rhodanese domain.

Domain

The DSP10 (MKP5) has two domains: rhodanese domain and phosphatase domain. The rhodanese domain can bind to kinases [1]. Drosophila has lost the whole rhodanese domain.

Function

Human DUSP10 is a phosphatase specific for p38 and JNK. It binds to and inactivates p38 and JNK, but not 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 its expression in cultured cells is elevated by stress stimuli [2, 3, 4].

On the other hand, it has been reported that human 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].

Human DUSP10 (MKP5) also has an immune role. It functions in the type I interferon system responding to viral infection. It interacts with, dephosphorylates and inactivates Interferon regulatory factor 3 (IRF3), an interferon regulatory factor which plays an important role in the type I interferon system. Increased type I interferon responses were observed in DUSP10/MKP5-deficient cells and animals upon various RNA virus infection, including H1N1 influenza virus, vesicular stomatitis virus and sendai virus [7]. DUSP10/MKP5 also regulates adipose tissue inflammation and insulin resistance [8].

References

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