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DUSP8  -  dual specificity phosphatase 8

Homo sapiens

Synonyms: C11orf81, Dual specificity protein phosphatase 8, Dual specificity protein phosphatase hVH-5, FLJ42958, HB5, ...
 
 
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Disease relevance of DUSP8

  • Among these is the human homologue of vaccinia virus H1 phosphatase gene clone 5 (hVH-5) product, which dephosphorylates and thus inhibits members of the MAPK family [1].
  • Because this variant of hVH-5 lacked intronic sequences in its genomic structure, we suggest it might be a processed pseudogene of hVH-5. psihVH-5 transcripts were detected in human peripheral tissues as well as in 11 of 14 breast cancer cell lines [1].
  • To determine the frequency of vertical transmission of hepatitis B antigen (HB5 Ag) from asymptomatic carrier mothers in Taiwan to their offspring, HB5 Ag was sought by radioimmunoassay and complement fixation [2].
  • Extensive and selective mutation of a rearranged VH5 gene in human B cell chronic lymphocytic leukemia [3].
  • Molecular evolution of the human immunoglobulin E response: high incidence of shared mutations and clonal relatedness among epsilon VH5 transcripts from three unrelated patients with atopic dermatitis [4].
 

High impact information on DUSP8

  • Three inter-related factors were found to increase the risk that antigenemia would develop in the infant: a high maternal complement-fixation titer for HB5 Ag: presence of HB5 Ag in the baby's umbilical-cord blood: and antigenemia in siblings [2].
  • The extent and nature of these mutations contrasts markedly from the low level of mutations noted in VH5 genes used by normal B cells or other Ig V genes found expressed in CLL [5].
  • Lack of extensive mutations in the VH5 genes used in common B cell chronic lymphocytic leukemia [5].
  • Southern blot hybridization studies with probes for VH251 and the JH locus revealed that only 7 (10%) of the 68 monoclonal CLL cell populations had undergone Ig gene rearrangement involving VH5 genes [5].
  • Two (3%) were found to have functionally rearranged VH5 genes that shared > or = 98% sequence homology with 5-2R1, a VH251 gene isolated from a pre-B cell acute lymphocytic leukemia [5].
 

Chemical compound and disease context of DUSP8

 

Biological context of DUSP8

 

Anatomical context of DUSP8

  • Another feature that distinguished hVH-5 from related phosphatases was that hVH-5 was expressed predominantly in the adult brain, heart, and skeletal muscle [8].
  • 2. Although 11p15.5 is an imprinted region, HB5 is almost entirely unmethylated on both alleles in lymphocytes [9].
  • Here, we analyzed hVH-5 transcripts in mammary carcinoma cell lines and discovered a sequence with 88% similarity to hVH-5 transcripts [1].
  • We have found a novel 1.2-kb VH5 gene transcript in normal fetal liver and cord blood and in transformed B lineage cells [10].
  • 4. The synergistic effect of CR2 was also observed with avidin as the cross-linking reagent for bound biotinylated HB5 and DA4.4, occurred in the presence of EGTA, and did not require T cells [11].
 

Associations of DUSP8 with chemical compounds

  • A unique proline-rich region distinguished hVH-5 from other closely related protein tyrosine phosphatases [8].
  • 0. The acid stabilization of insulin's conformation was attributed to the protonation of histidine at position 5 on the B-chain (HB5) as determined by 1H-NMR of the histidines, selective amino acid alteration, and enthalpies of ionization [12].
  • Expression of HB5 and HF2 antigens was down-regulated during cellular differentiation of G3 cells by retinoic acid or N,N'-hexamethylene-bis-acetamide treatment, whereas that of HE11 antigen was up-regulated with cellular differentiation by retinoic acid [13].
 

Other interactions of DUSP8

  • While most gene alterations seen with 2-DG and IR dual treatment were confirmed in the gene profiles seen with individual (2-DG or IR) treatments, several genes appeared differentially regulated between IR and 2-DG (e.g., DUSP8, IL8, GADD45B) [14].
 

Analytical, diagnostic and therapeutic context of DUSP8

  • Binding to SPA in ELISA occurred with 15 of 15 VH3 IgM, but none of 12 IgM from the VH1, VH4, VH5, or VH6 families [15].
  • Utilizing flow microfluorimetry analysis, epitopes recognized by anti-CR2 mAb HB5, OKB7, B2, and four other anti-CR2 antibodies were detected on CR2 expressing transfectants but not parental cells [16].
  • We subsequently selected stably transformed cells that expressed human CR2, as assessed by flow microfluorimetry analysis and immunoprecipitation of 125I-labeled surface membranes using the monoclonal anti-CR2 antibody, HB5 [16].
  • A control PCR with the same VH primers in combination with JH primers yielded only 1 of 13 sequences from VH5, indicating preferential VH5 usage only for IgE [17].
  • Of 9 proven anti-CD21 MAbs now examined on frozen sections of human nasopharynx, tonsil and ecto-cervix, only 3 (HB5, anti-B2, AB1) showed staining of stratified epithelium; 2 of these (HB5, anti-B2) also reacted with the surface of epithelial cells freshly dispersed from these sites [18].

References

  1. Identification of a transcriptionally active hVH-5 pseudogene on 10q22.2. Berger, I.R., Buschbeck, M., Bange, J., Ullrich, A. Cancer Genet. Cytogenet. (2005) [Pubmed]
  2. Vertical transmission of hepatitis B antigen in Taiwan. Stevens, C.E., Beasley, R.P., Tsui, J., Lee, W.C. N. Engl. J. Med. (1975) [Pubmed]
  3. Extensive and selective mutation of a rearranged VH5 gene in human B cell chronic lymphocytic leukemia. Cai, J., Humphries, C., Richardson, A., Tucker, P.W. J. Exp. Med. (1992) [Pubmed]
  4. Molecular evolution of the human immunoglobulin E response: high incidence of shared mutations and clonal relatedness among epsilon VH5 transcripts from three unrelated patients with atopic dermatitis. van der Stoep, N., van der Linden, J., Logtenberg, T. J. Exp. Med. (1993) [Pubmed]
  5. Lack of extensive mutations in the VH5 genes used in common B cell chronic lymphocytic leukemia. Rassenti, L.Z., Kipps, T.J. J. Exp. Med. (1993) [Pubmed]
  6. Hairy leukoplakia: Epstein-Barr virus receptors on oral keratinocyte plasma membranes. Corso, B., Eversole, L.R., Hutt-Fletcher, L. Oral Surg. Oral Med. Oral Pathol. (1989) [Pubmed]
  7. Investigation of DUSP8 and CALCA in alcohol dependence. Hink, R.L., Hokanson, J.E., Shah, I., Long, J.C., Goldman, D., Sikela, J.M. Addiction biology. (2003) [Pubmed]
  8. hVH-5: a protein tyrosine phosphatase abundant in brain that inactivates mitogen-activated protein kinase. Martell, K.J., Seasholtz, A.F., Kwak, S.P., Clemens, K.K., Dixon, J.E. J. Neurochem. (1995) [Pubmed]
  9. 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. Nesbit, M.A., Hodges, M.D., Campbell, L., de Meulemeester, T.M., Alders, M., Rodrigues, N.R., Talbot, K., Theodosiou, A.M., Mannens, M.A., Nakamura, Y., Little, P.F., Davies, K.E. Genomics (1997) [Pubmed]
  10. Structure and expression of human germline VH transcripts. Berman, J.E., Humphries, C.G., Barth, J., Alt, F.W., Tucker, P.W. J. Exp. Med. (1991) [Pubmed]
  11. Synergistic interaction between complement receptor type 2 and membrane IgM on B lymphocytes. Carter, R.H., Spycher, M.O., Ng, Y.C., Hoffman, R., Fearon, D.T. J. Immunol. (1988) [Pubmed]
  12. Acid stabilization of insulin. Bryant, C., Spencer, D.B., Miller, A., Bakaysa, D.L., McCune, K.S., Maple, S.R., Pekar, A.H., Brems, D.N. Biochemistry (1993) [Pubmed]
  13. Establishment of three monoclonal antibodies specific for prespermatogonia and intratubular malignant germ cells in humans. Hiraoka, N., Yamada, T., Abe, H., Hata, J. Lab. Invest. (1997) [Pubmed]
  14. Altered gene expression induced by ionizing radiation and glycolytic inhibitor 2-deoxy-glucose in a human glioma cell line: implications for radio sensitization. Heminger, K., Jain, V., Kadakia, M., Dwarakanath, B., Berberich, S.J. Cancer Biol. Ther. (2006) [Pubmed]
  15. The structural basis of germline-encoded VH3 immunoglobulin binding to staphylococcal protein A. Hillson, J.L., Karr, N.S., Oppliger, I.R., Mannik, M., Sasso, E.H. J. Exp. Med. (1993) [Pubmed]
  16. Analysis of epitope expression and the functional repertoire of recombinant complement receptor 2 (CR2/CD21) in mouse and human cells. Carel, J.C., Frazier, B., Ley, T.J., Holers, V.M. J. Immunol. (1989) [Pubmed]
  17. Analysis of Ig VH region genes encoding IgE antibodies in splenic B lymphocytes of a patient with asthma. Snow, R.E., Chapman, C.J., Frew, A.J., Holgate, S.T., Stevenson, F.K. J. Immunol. (1995) [Pubmed]
  18. Identification of a human epithelial cell surface protein sharing an epitope with the C3d/Epstein-Barr virus receptor molecule of B lymphocytes. Young, L.S., Dawson, C.W., Brown, K.W., Rickinson, A.B. Int. J. Cancer (1989) [Pubmed]
 
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