Phosphatase Subfamily DSP15

Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily DSP15

DSP15 subfamily emerged in metazoan and duplicated in vertebrates. It is characterized by a N-termnal myristoylation site which targets it to plasma membrane. Little is known about its molecular function.

Evolution

DSP15 subfamily is found across metazoa, and likely homologs exist in even in several protist lineages. It usually has a single copy in invertebrate genomes and two copies in vertebrate genomes (DUSP15 and DUSP22 in human).

Domain

DSP15 has a N-terminal myristoylation site and a phosphatase domain. The two members in human genome DUSP15 and DUSP22 are myristoylated at Gly-2. The myristoylation site targets the protein to plasma memrane. Mutation of the myristoylation site Gly-2 of DUSP15 abrogated membrane location [1].

Functions

DUSP15 (VHY)

Human DUSP15 is specifically expressed in testis [1] (also see GTEx portal). However, DUSP15 has also been reported to be transcriptionally regulated during oligodendrocyte differentiation and in multiple sclerosis lesions, in which DUSP15 dephosphorylates PDGFR-beta and SNX6 [2].

DUSP22 (VHX/JKAP/JSP1/LMW-DSP2)

Different from DUSP15, human DUSP22 is expressed in various tissues (see GTEx portal).

DUSP22 localizes in the actin filament-enriched region. Expression of DUSP22 reduced cell migration, whereas a DUSP22 mutant lacking catalytic activity promoted cell motility. DUSP22 dephosphorylates tyrosines 397, 576, and 577 of focal adhesion kinase (FAK) [3]. DUSP22 also dephosphorylates Ser-118 of estrogen receptor-alpha (ER-alpha) therefore regulating ER-alpha-mediated signaling [4].

Unexpectedly, DUSP22 is a positive rather than negative regulatory of JNK pathway. It did not interact with or dephosphorylate JNK in vitro, suggesting that DUSP22 exerts its effect on JNK in an indirect manner [5, 6].

DUSP22 may have other functions. It inhibits (may or may not by directly dephospho rylation) PKA activity and thereby determines TAU phosphorylation status and CREB signaling [7]. It also acts as a negative regulator (may or may not by directly dephospho rylation) of the IL-6/LIF/STAT3-mediated signaling pathway [8].

DUSP22 may represent a tumor-suppressor gene, since its loss may contribute to the pathogenesis of cutaneous anaplastic large-cell lymphomas (ALCLs) according to clinic cases [9].

References

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