Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antifreeze glycopeptides (AFGP) have been isolated from the fully pelagic high-Antarctic silverfish Pleuragramma antarcticum of the suborder Notothenioidei (Perciformes). The fishes were caught during the PRV Polarstern expedition EPOS III (Jan-Mar, 1989) in the eastern and southeastern Weddell Sea. Glycoconjugate and amino acid analysis of antifreeze glycopeptides (AFGP) indicate that the glycopeptide structure is identical to the polymers of H2N[Ala-Ala(beta-galactosyl(1-->3)-alpha-N- acetylgalactosamine)Thr]nAla-Ala-COOH of previously studied Antarctic notothenioids. The content of AFGPs in P. antarcticum is lower than in other notothenioid fish from the same region. Antifreeze activity shows a maximal hysteresis of 1.19 degrees C at a concentration of 20 mg/ml AFGP. A linear increase in activity of the antifreeze glycopeptides could be demonstrated concomittant with a decreasing ice content. The freezing point of blood serum is -1.9 degrees C.
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PMID:Antifreeze glycopeptides of the high-Antarctic silverfish Pleuragramma antarcticum (Notothenioidei). 765 79

We investigated the function of antigenic domains on gI in virulence and immunogenicity. Three PRV gI mutants were constructed by deleting nucleotides coding for the following amino acids: valine-125 and cysteine-126, located in a discontinuous antigenic domain (M 303); glycine-59 and aspartic acid-60 located in a continuous antigenic domain (M304); and arginine-67 and alanine-68, located in a discontinuous antigenic domain (M305). Mismatch primers in the polymerase chain reaction were used to introduce the deletions. Anti-gI monoclonal antibodies were used in an immunoperoxidase monolayer assay to distinguish PRV gI mutants from wild-type PRV. The gI mutant viruses were tested for their growth in vitro and for their virulence in mice. The growth properties of PRV gI mutant virus M303 were comparable to the growth properties of a PRV gI-negative mutant (M301): both mutants produced small plaques in various cells, and when grown on swine kidney cells and chicken embryo fibroblasts, their growth was disadvantaged compared to wild-type PRV. However, in embryonal Balb/c mouse cells expressing gI, gI mutant viruses and wild-type PRV produced plaques of the same size, confirming that the mutations in gI are responsible for the small plaque phenotype. The growth properties of PRV gI mutant viruses M 304 and M 305 were comparable to the growth properties of wild-type PRV. When the mean time to death was used as the criterion, the gI mutant viruses M 301 and M 303 were significantly less virulent in mice than wild-type PRV. Four other, independently obtained, PRV mutants all carrying the valine-125 and cysteine-126 deletion (M 308, M 309, M 310 and M 311 respectively) exhibit the same phenotype. Our results show that deleting valine-125 and cysteine-126 in gI decreases plaque size and reduces virulence in mice to the same degree as deleting the gI protein.
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PMID:Deleting valine-125 and cysteine-126 in glycoprotein gI of pseudorabies virus strain NIA-3 decreases plaque size and reduces virulence in mice. 839 68

The JAK2 V617F mutation present in over 95% of Polycythemia Vera patients and in 50% of Essential Thrombocythemia and Primary Myelofibrosis patients renders the kinase constitutively active. In the absence of a three-dimensional structure for the full-length protein, the mechanism of activation of JAK2 V617F has remained elusive. In this study, we used functional mutagenesis to investigate the involvement of the JH2 alphaC helix in the constitutive activation of JAK2 V617F. We show that residue F595, located in the middle of the alphaC helix of JH2, is indispensable for the constitutive activity of JAK2 V617F. Mutation of F595 to Ala, Lys, Val or Ile significantly decreases the constitutive activity of JAK2 V617F, but F595W and F595Y are able to restore it, implying an aromaticity requirement at position 595. Substitution of F595 to Ala was also able to decrease the constitutive activity of two other JAK2 mutants, T875N and R683G, as well as JAK2 K539L, albeit to a lower extent. In contrast, the F595 mutants are activated by erythropoietin-bound EpoR. We also explored the relationship between the dimeric conformation of EpoR and several JAK2 mutants. Since residue F595 is crucial to the constitutive activation of JAK2 V617F but not to initiation of JAK2 activation by cytokines, we suggest that small molecules that target the region around this residue might specifically block oncogenic JAK2 and spare JAK2 wild-type.
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PMID:JAK2 V617F constitutive activation requires JH2 residue F595: a pseudokinase domain target for specific inhibitors. 2058 91