PMID: 9531494Jun 11, 1998Paper

Activation of S6 kinase in human neutrophils by calcium pyrophosphate dihydrate crystals: protein kinase C-dependent and phosphatidylinositol-3-kinase-independent pathways

The Biochemical Journal
Christopher TudanH M Burt

Abstract

Phosphatidylinositol 3-kinase (PI 3-kinase) has been shown previously to be a central enzyme in crystal-induced neutrophil activation. Since activation of the 70 kDa S6 kinase (p70S6K) has been shown to be dependent on PI 3-kinase activation in mammalian cells, and since the former is a key enzyme in the transmission of signals to the cell nucleus, activation of p70(S6K) was investigated in crystal-stimulated neutrophils. Cytosolic fractions from calcium pyrophosphate dihydrate (CPPD)-crystal-activated neutrophils were separated by Mono Q chromatography and analysed for phosphotransferase activity using a range of substrates and probed by Western analysis using antibodies to p70(S6K) and mitogen-activated protein kinase (MAP kinase). CPPD crystals induced a robust, transient activation (peak activity at 2 min) of p70(S6K) that was fully inhibited by pretreatment with rapamycin. This is the first report of the activation of p70(S6K) in neutrophil signal transduction pathways induced by an agonist. This crystal-induced activation of p70(S6K) could also be inhibited by a protein kinase C (PKC) inhibitor (Compound 3), but not by the PI 3-kinase inhibitor wortmannin. CPPD crystals also activated the ERK1 and ERK2 forms of MAP kinase...Continue Reading

Citations

May 24, 2006·Rheumatic Diseases Clinics of North America·E S Molloy, G M McCarthy
Dec 27, 2005·The Journal of Surgical Research·Masayasu IwaseMasao Nagumo
May 12, 2004·Current Rheumatology Reports·Eamonn S Molloy, Geraldine M McCarthy
Dec 21, 2000·Current Rheumatology Reports·G M McCarthy
Apr 3, 2009·Current Opinion in Rheumatology·Hang-Korng Ea, Frédéric Lioté
May 1, 2002·Current Opinion in Rheumatology·Maria P Morgan, Geraldine M McCarthy
Aug 10, 2002·American Journal of Physiology. Endocrinology and Metabolism·Richard L BradleyBentley Cheatham
Dec 3, 2002·Biochemical and Biophysical Research Communications·Carmen González-Yanes, Víctor Sánchez-Margalet
Jul 2, 2005·Joint, Bone, Spine : Revue Du Rhumatisme·Ru Liu-Bryan, Frédéric Lioté

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