Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Receptor-linked phosphatidylinositol (PtdIns) 3-kinase may generate a second-messenger signal. Here a large-scale purification of the bovine brain enzyme, based on methods developed by Morgan, Smith and Parker [(1990) Eur. J. Biochem. 191, 761-767] and Fry, Panayotou, Dhand, Ruiz-Larrea, Gout, Nguyen, Courtneidge and Waterfield [(1992) Biochem. J. 288, 383-393] is described. The purified enzyme is shown to be a heterodimer of 85 kDa and 110 kDa protein subunits (p85 and p110). Labelling with 5'-p-fluorosulphonylbenzoyladenosine shows that p110 contains an ATP-binding site and confers catalytic activity to the complex. The purified complex is known to be highly phosphorylated on both p85 alpha and p110 subunits, and dephosphorylation generates a deactivated complex, indicating that phosphorylation is an important covalent modification of the complex and may modulate PtdIns 3-kinase activity.
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PMID:Characterization of the bovine brain cytosolic phosphatidylinositol 3-kinase complex. 838 68

The deposition of monosodium urate (MSU) crystals in the joints of humans leads to an extremely acute, inflammatory reaction, commonly known as gout, characterized by a massive infiltration of neutrophils. Direct interactions of MSU crystals with human neutrophils and inflammatory mediators are crucial to the induction and perpetuation of gout attacks. The intracellular signaling events initiated by the physical interaction between MSU crystals and neutrophils depend on the activation of specific tyrosine kinases (Src and Syk, in particular). In addition, PI-3Ks may be involved. The present study investigates the involvement of the PI-3K family in the mediation of the responses of human neutrophils to MSU crystals. The results obtained indicate that the interaction of MSU crystals with human neutrophils leads to the stimulation of class Ia PI-3Ks by a mechanism that is dependent on the tyrosine kinase Syk. We also found an increase in the amount of p85 associated with the Nonidet P-40-insoluble fraction derived from MSU crystal-stimulated human neutrophils. Furthermore, MSU crystals induce the formation of a complex containing p85 and Syk, which is mediated by the Src family kinases. Finally, evidence is also obtained indicating that the activation of PI-3Ks by MSU crystals is a critical element regulating phospholipase D activation and degranulation of human neutrophils. The latter response is likely to be involved in the joint and tissue damage that occurs in gouty patients.
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PMID:Crystal-induced neutrophil activation. IX. Syk-dependent activation of class Ia phosphatidylinositol 3-kinase. 1753 83