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Träfflista för sökning "WFRF:(Welsh J) srt2:(2000-2004)"

Sökning: WFRF:(Welsh J) > (2000-2004)

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  • Cross, Michael J, et al. (författare)
  • The Shb Adaptor Protein Binds to Tyrosine 766 in the FGFR-1 and Regulatesthe Ras/MEK/MAPK Pathway via FRS2 Phosphorylation in Endothelial Cells
  • 2002
  • Ingår i: Molecular Biology of the Cell. - 1059-1524 .- 1939-4586. ; 13:8, s. 2881-2893
  • Tidskriftsartikel (refereegranskat)abstract
    • Stimulation of fibroblast growth factor receptor-1 (FGFR-1) is known to result in phosphorylation of tyrosine 766 and the recruitment and subsequent activation of phospholipase C-γ (PLC-γ). To assess the role of tyrosine 766 in endothelial cell function, we generated endothelial cells expressing a chimeric receptor, composed of the extracellular domain of the PDGF receptor-α and the intracellular domain of FGFR-1. Mutation of tyrosine 766 to phenylalanine prevented PLC-γ activation and resulted in a reduced phosphorylation of FRS2 and reduced activation of the Ras/MEK/MAPK pathway relative to the wild-type chimeric receptor. However, FGFR-1–mediated MAPK activation was not dependent on PKC activation or intracellular calcium, both downstream mediators of PLC-γ activation. We report that the adaptor protein Shb is also able to bind tyrosine 766 in the FGFR-1, via its SH2 domain, resulting in its subsequent phosphorylation. Overexpression of an SH2 domain mutant Shb caused a dramatic reduction in FGFR-1–mediated FRS2 phosphorylation with concomitant perturbment of the Ras/MEK/MAPK pathway. Expression of the chimeric receptor mutant and the Shb SH2 domain mutant resulted in a similar reduction in FGFR-1–mediated mitogenicity. We conclude, that Shb binds to tyrosine 766 in the FGFR-1 and regulates FGF-mediated mitogenicity via FRS2 phosphorylation and the subsequent activation of the Ras/MEK/MAPK pathway.
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  • Jones, MG, et al. (författare)
  • Association of HLA-DQ5 and HLA-DR1 with sensitization to organic acidanhydrides
  • 2004
  • Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222. ; 34:5, s. 812-816
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Organic acid anhydrides are low molecular weight industrial chemicals, able to cause rhinoconjunctivitis and asthma associated with specific IgE against hapten-carrier protein conjugate. Only a proportion of exposed workers develop IgE-associated allergy to acid anhydrides. Objective We determined whether genetic susceptibility, in particular, HLA Class II alleles may be a risk factor. Methods We undertook HLA typing in 52 cases who had confirmed specific IgE and in 73 referents matched on site, age and duration of acid anhydride exposure identified in cross-sectional studies of workers exposed to hexahydrophthalic (HHPA), methylhexahydrophthalic (MHHPA) and methyltetrahydrophthalic (MTHPA) anhydrides. Results The linked alleles DQ5 (odds ratio [OR]=4.3; 95% confidence interval [95% CI]=1.7, 11) and DR1 (OR 3.0; 95% CI 1.2, 11) were more prevalent in cases than in referents. Within DQ5, DQB1*0501 was particularly frequent (OR 3.0; 95% CI 1.2, 7.4). Conclusion DQB1*05 gene confers susceptibility to develop specific IgE antibodies against HHPA, MHHPA and a non-significant trend with MTHPA. DQB1*0501 is protective for other low molecular chemical sensitizers (isocyanates and plicatic acid) which may indicate varying affinities for the corresponding specific class II molecules.
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  • Resultat 1-10 av 24

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