Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Localized juvenile periodontitis (ljp) is an early onset form of periodontal disease characterized by unique localization to first molars and incisors and a high prevalence of neutrophil abnormalities, particularly chemotaxis. The intracellular transduction mechanisms that follow receptor-ligand coupling on the neutrophil surface and lead to chemotaxis are not clearly established. Chemotaxis and phagocytosis are modulated by a variety of receptors and involve several activation pathways; the role of intracellular calcium as a presumptive second messenger and mediator of these events is well established. The putative effector mechanisms for the chemotactic receptor of neutrophils also include the possible activation of a phospholipase, protein kinase C, methyltransferase, or adenylate cyclase. In normal neutrophils, a phosphoinositide pathway initiated by phospholipase C, which results in the activation of protein kinase C via diacylglycerol and the generation of IP3, has been implicated. In order to better understand the stages of neutrophil transduction, fluorescent probes were used to monitor neutrophil calcium changes. Chlorotetracycline (CTC) was used as an indirect probe of intracellular membrane-bound pool of calcium stores, and Quin-2 was used to monitor cytosolic free calcium levels of FMLP stimulated normal and LJP neutrophils. The results indicate that the early phase of the calcium response affiliated with the release of intracellularly sequestered calcium appears intact in LJP neutrophils, as the CTC fluorescence changes were similar to control values. The second phase of the calcium response, associated with membrane channel activation and an influx of extracellular calcium, appeared compromised in the neutrophils of the LJP population.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Defective chemotaxis and calcium response in localized juvenile periodontitis neutrophils. 839 75

The formyl peptide receptor (FPR) is a prototypical chemoattractant receptor expressed in neutrophils. It is well known that the FPR couples to G(i) proteins to activate phospholipase C, chemotaxis, and cytotoxic cell functions, but the in vivo role of the FPR in man has remained elusive. Recently, F110S and C126W mutations of the FPR have been associated with localized juvenile periodontitis. We studied FPR-F110S and FPR-C126W in comparison with wild-type FPR (FPR-WT) by coexpressing epitope-tagged versions of these receptors with the G protein Galpha(i2)beta(1)gamma(2) in Sf9 insect cells. FPRs were efficiently expressed in Sf9 membranes as assessed by immunoblotting using the beta(2)-adrenoreceptor as a standard. FPR-C126W differed from FPR-WT and FPR-F110S in migration on SDS-polyacrylamide gels and tunicamycin-sensitive glycosylation. FPR-WT efficiently reconstituted high-affinity agonist binding and agonist- and inverse agonist-regulated guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) binding to Galpha(i2)beta(1)gamma(2). In contrast, FPR-F110S only weakly reconstituted agonist-stimulated GTPgammaS binding, and FPR-C126W was completely inefficient. Collectively, our data show almost complete and complete loss of G(i) protein coupling in FPR-F110S and FPR-C126W, respectively. The severe functional defects in FPR-F110S and FPR-C126W contrast with the discrete clinical symptoms associated with these mutations, indicating that loss of FPR function in host defense is, for the most part, readily compensated.
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PMID:Defective Gi protein coupling in two formyl peptide receptor mutants associated with localized juvenile periodontitis. 1155 6