PMID: 9440544Jan 24, 1998Paper

Granulocyte-macrophage colony-stimulating factor and IL-5 activate mitogen-activated protein kinase through Jak2 kinase and phosphatidylinositol 3-kinase in human eosinophils

The Journal of Allergy and Clinical Immunology
M HiraguriI Iwamoto

Abstract

Mitogen-activated protein (MAP) kinases are activated by the sequential activation of Ras, Raf, and MEK (MAP kinase kinase) and regulate a wide variety of cell functions. To determine the kinase cascade for granulocyte-macrophage colony-stimulating factor (GM-CSF)- and IL-5-induced MAP kinase activation in eosinophils, we studied the effect of inhibitors of Jak2 kinase, tyrosine kinases, phosphatidylinositol 3-kinase, and protein kinase C on GM-CSF- and IL-5-induced MAP kinase activation in human eosinophils. GM-CSF and IL-5 activated 40, 42, and 44 kilodalton MAP kinase isoforms in eosinophils. This was indicated by the electrophoretic mobility shift of the three isoforms of MAP kinase in immunoblotting with anti-MAP kinase antibody and also by in-gel MAP kinase assay. MAP kinase activation was time- and dose-dependent, becoming maximal 3 to 15 minutes after stimulation. A Jak2 kinase inhibitor AG-490, a tyrosine kinase inhibitor genistein, and a phosphatidylinositol 3-kinase inhibitor wortmannin inhibited GM-CSF- and IL-5-induced MAP kinase activation in eosinophils, whereas a protein kinase C inhibitor staurosporine had a weak inhibitory effect. Furthermore, AG-490 and genistein prevented GM-CSF-induced tyrosine phosphorylat...Continue Reading

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Citations

Mar 29, 2000·Biochemical and Biophysical Research Communications·K KumanoI Iwamoto
May 5, 1999·Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology·T LalaniA R Ahmed
Jun 18, 2002·Immunopharmacology and Immunotoxicology·Chun Kwok WongChristopher Wai Kei Lam
Oct 31, 2002·American Journal of Respiratory and Critical Care Medicine·Wei DuanW S Fred Wong
Dec 1, 2001·Expert Opinion on Biological Therapy·K BlümchenE Hamelmann
Apr 24, 2007·Veterinary Immunology and Immunopathology·Marianela C SerradellDiana T Masih
Apr 14, 2004·Critical Reviews in Clinical Laboratory Sciences·Chun Kwok WongChristopher Wai Kei Lam
May 5, 1999·Current Opinion in Hematology·G J Roboz, S Rafii

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