Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human lymphocytes were challenged with reactive oxygen species (ROS) generated by xanthine/xanthine oxidase leading to an increase in tyrosine phosphorylation, together with an increase in tyrosine phosphatase activity. In the presence of 50 microM vanadate and xanthine/xanthine oxidase, tyrosine phosphatase activity was inhibited and a marked increase in tyrosine phosphorylation was observed. The addition of catalase abolished the increase in tyrosine phosphorylation while the addition of superoxide dismutase had no effect. This suggests that vanadate together with hydrogen peroxide derived from xanthine/xanthine oxidase activity, interact to produce an agent that is an effective inhibitor of tyrosine phosphatase activity. When human lymphocytes were challenged with xanthine/xanthine oxidase in the presence of 50 microM CuCl2, an increase in both tyrosine phosphatase and kinase activity was observed. Cupric ions inhibited xanthine oxidase activity by 84%; neither superoxide or hydroxyl radicals could be detected, but traces of hydrogen peroxide were detected in the medium. We conclude that unbound metals can interact with ROS and readily influence signalling mechanisms in human lymphocytes.
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PMID:Free radical stimulation of tyrosine kinase and phosphatase activity in human peripheral blood mononuclear cells. 953 75

Previous studies demonstrated that ICAM-1 ligation on human pulmonary microvascular endothelial cells (ECs) sequentially induces activation of xanthine oxidase and p38 MAPK. Inhibition of these signaling events reduces neutrophil migration to the EC borders. This study examined the role of SRC tyrosine kinases in ICAM-1-initiated signaling within these ECs. Cross-linking ICAM-1 on tumor necrosis factor-alpha-pretreated ECs induced an increase in the activity of SRC tyrosine kinases. This increase was inhibited by allopurinol (a xanthine oxidase inhibitor), Me2SO (a hydroxyl radical scavenger), or deferoxamine (an iron chelator). Phenylarsine oxide, a tyrosine phosphatase inhibitor, reduced the base-line activity of SRC as well as the increase in SRC activity induced by ICAM-1 cross-linking. Specific inhibition of the protein expression of the SRC homology 2-containing protein-tyrosine phosphatase-2 (SHP-2) by an antisense oligonucleotide prevented the induced SRC activation but had no effect on the basal SRC activity. Activation of SRC tyrosine kinases was accompanied by tyrosine phosphorylation of ezrin at Tyr-146, which was inhibited by PP2, an SRC tyrosine kinase inhibitor. Moreover, PP2 completely inhibited p38 activation, suggesting a role for SRC tyrosine kinases in p38 activation. These data demonstrate that ICAM-1 ligation activates SRC tyrosine kinases and that this activation requires SHP-2 as well as production of reactive oxygen species generated from xanthine oxidase. Activation of SRC tyrosine kinases in turn leads to tyrosine phosphorylation of ezrin, as well as activation of p38, a kinase previously identified to be required for cytoskeletal changes induced by ICAM-1 ligation and for neutrophil migration along the EC surface.
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PMID:Activation of SRC tyrosine kinases in response to ICAM-1 ligation in pulmonary microvascular endothelial cells. 1450 78