Alternative titles; symbols
HGNC Approved Gene Symbol: DUSP8
Cytogenetic location: 11p15.5 Genomic coordinates (GRCh38): 11:1,554,051-1,572,848 (from NCBI)
Dual-specificity phosphatases (DUSPs) constitute a large heterogeneous subgroup of the type I cysteine-based protein-tyrosine phosphatase superfamily. DUSPs are characterized by their ability to dephosphorylate both tyrosine and serine/threonine residues. DUSP8 belongs to a class of DUSPs, designated MKPs, that dephosphorylate MAPK (mitogen-activated protein kinase) proteins ERK (see 601795), JNK (see 601158), and p38 (see 600289) with specificity distinct from that of individual MKP proteins. MKPs contain a highly conserved C-terminal catalytic domain and an N-terminal Cdc25 (see 116947)-like (CH2) domain. MAPK activation cascades mediate various physiologic processes, including cellular proliferation, apoptosis, differentiation, and stress responses (summary by Patterson et al., 2009).
In a screen for PTPases, Martell et al. (1995) isolated a novel clone for DUSP8, which they termed HVH5. They cloned the full-length cDNA from a human fetal brain library and found that it encodes a deduced 625-amino acid polypeptide. The protein sequence contained several predicted sites for phosphorylation by protein kinases. By Northern blot analysis, they showed that the gene was expressed as mRNAs of 5.5 and 2.5 kb, which were highly abundant in adult brain and also present in heart and skeletal muscle. In situ hybridization to an e16.5 mouse embryo showed expression in the developing brain, spinal cord, and ganglia.
Nesbit et al. (1997) analyzed the genomic structure of DUSP8 and found that the gene has 6 exons spanning 13 kb of the genome.
By fluorescence in situ hybridization, Nesbit et al. (1997) mapped the DUSP8 gene to chromosome 11p15.5. They noted that loss of heterozygosity in this region has been associated with a number of tumor types.
Nesbit et al. (1997) noted that DUSP8 has an intronless pseudogene at chromosome 10q11.2.
Martell et al. (1995) expressed the HVH5 protein and showed that it had phosphatase activity. They determined that HVH5 expression could be induced in PC12 cells upon stimulation by nerve growth factor or insulin.
Martell, Karen J., Seasholtz, A. F., Kwak, S. P., Clemens, K. K., Dixon, J. E. hVH-5: a protein tyrosine phosphatase abundant in brain that inactivates mitogen-activated protein kinase. J. Neurochem. 65: 1823-1833, 1995. [PubMed: 7561881] [Full Text: https://doi.org/10.1046/j.1471-4159.1995.65041823.x]
Nesbit, M. A., Hodges, M. D., Campbell, L., de Meulemeester, T. M. A. M. O., Alders, M., Rodrigues, N. R., Talbot, K., Theodosiou, A. M., Mannens, M. A., Nakamura, Y., Little, P. F. R., Davies, K. E. Genomic organization and chromosomal localization of a member of the MAP kinase phosphatase gene family to human chromosome 11p15.5 and a pseudogene to 10q11.2. Genomics 42: 284-294, 1997. [PubMed: 9192849] [Full Text: https://doi.org/10.1006/geno.1997.4737]
Patterson, K. I., Brummer, T., O'Brien, P. M., Daly, R. J. Dual-specificity phosphatases: critical regulators with diverse cellular targets. Biochem. J. 418: 475-489, 2009. [PubMed: 19228121] [Full Text: https://doi.org/10.1042/bj20082234]