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Am J Physiol Lung Cell Mol Physiol 278: L59-L67, 2000;
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Vol. 278, Issue 1, L59-L67, January 2000

Protein kinase C is involved in enhanced airway smooth muscle cell growth in hyperresponsive rats

M. E. Zacour and J. G. Martin

Meakins-Christie Laboratories and the Heisler Laboratory of the Montreal Chest Institute Research Centre, McGill University, Montreal, Quebec, Canada H2X 2P2

Fischer rat airway smooth muscle (ASM) models two potential risk factors for asthma: hyperresponsiveness to contractile agonists and to growth stimuli. The aim of this study was to identify the mechanisms responsible for enhanced ASM mitogenic response in Fischer rats compared with the control Lewis strain. The enhanced Fischer ASM cell growth response to fetal bovine serum (FBS) could not be accounted for by phospholipase C, mitogen-activated protein kinases, or tyrosine kinase activities as assessed by pharmacological inhibition and Western blotting. In contrast, depletion of phorbol ester-sensitive isoforms of the serine/threonine kinase protein kinase C (PKC) removed the difference in growth response between the rat strains. Additionally, FBS selectively induced serine/threonine phosphorylation of a 115-kDa protein in Fischer ASM cells. Enhanced activation of PKC-beta I and decreased activation of PKC-delta in Fischer compared with Lewis cells following FBS stimulation were suggested by Western blotting of membrane and cytosolic fractions. The data are consistent with a role for PKC in the enhanced ASM cell growth of hyperresponsive rats.

proliferation; epidermal growth factor; tyrosine phosphorylation; serine/threonine phosphorylation; U-73122


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