Alternative titles; symbols
HGNC Approved Gene Symbol: DUSP2
Cytogenetic location: 2q11.2 Genomic coordinates (GRCh38) : 2:96,143,169-96,145,440 (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. DUSP2 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).
Rohan et al. (1993) isolated mouse and human cDNAs encoding DUSP2, which they called PAC1, a mitogen-induced 32-kD protein that contains a sequence that is associated with enzymatic activity in previously identified protein phosphotyrosine phosphatases. The predicted human PAC1 protein has 314 amino acids. Northern blot analysis of human cell lines and mouse tissues revealed that PAC1 is expressed predominantly in hematopoietic tissues. By immunofluorescence of transfected cells and mitogen-stimulated T cells, Rohan et al. (1993) localized PAC1 to the nucleus.
Yi et al. (1995) determined that the PAC1 (DUSP2) gene contains 4 exons that span approximately 2.3 kb.
By somatic cell hybrid analysis, linkage analysis, and in situ hybridization, Yi et al. (1995) mapped the PAC1 gene to chromosome 2p11.2-q11. Using fluorescence in situ hybridization, Martell et al. (1994) refined the localization of the PAC1 gene to chromosome 2q11.
Ward et al. (1994) demonstrated that PAC1 is a dual-specific thr/tyr phosphatase that is a physiologically relevant MAP kinase phosphatase.
Yin et al. (2003) showed that during apoptosis, p53 (191170) activates transcription of PAC1 by binding to a palindromic site in the PAC1 promoter. PAC1 transcription is induced in response to serum deprivation and oxidative stress, which results in p53-dependent apoptosis, but not in response to gamma-irradiation, which causes cell cycle arrest. Reduction of PAC1 transcription using small interfering RNA inhibits p53-mediated apoptosis, whereas overexpression of PAC1 increases susceptibility to apoptosis and suppresses tumor formation. Moreover, Yin et al. (2003) found that activation of p53 significantly inhibited MAP kinase (see 602425) activity. They concluded that, under specific stress conditions, p53 regulates transcription of PAC1 through a new p53-binding site, and that PAC1 is necessary and sufficient for p53-mediated apoptosis.
Martell, K. J., Kwak, S., Hakes, D. J., Dixon, J. E., Trent, J. M. Chromosomal localization of four human VH1-like protein-tyrosine phosphatases. Genomics 22: 462-464, 1994. [PubMed: 7806236] [Full Text: https://doi.org/10.1006/geno.1994.1411]
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]
Rohan, P. J., Davis, P., Moskaluk, C. A., Kearns, M., Krutzsch, H., Siebenlist, U., Kelly, K. PAC-1: a mitogen-induced nuclear protein tyrosine phosphatase. Science 259: 1763-1766, 1993. [PubMed: 7681221] [Full Text: https://doi.org/10.1126/science.7681221]
Ward, Y., Gupta, S., Jensen, P., Wartmann, M., Davis, R. J., Kelly, K. Control of MAP kinase activation by the mitogen-induced threonine/tyrosine phosphatase PAC1. Nature 367: 651-654, 1994. [PubMed: 8107850] [Full Text: https://doi.org/10.1038/367651a0]
Yi, H., Morton, C. C., Weremowicz, S., McBride, O. W., Kelly, K. Genomic organization and chromosomal localization of the DUSP2 gene, encoding a MAP kinase phosphatase, to human 2p11.2-q11. Genomics 28: 92-96, 1995. [PubMed: 7590752] [Full Text: https://doi.org/10.1006/geno.1995.1110]
Yin, Y., Liu, Y.-X., Jin, Y. J., Hall, E. J., Barrett, J. C. PAC1 phosphatase is a transcription target of p53 in signalling apoptosis and growth suppression. Nature 422: 527-531, 2003. [PubMed: 12673251] [Full Text: https://doi.org/10.1038/nature01519]