Atp-stimulated smooth muscle cell proliferation requires
independent erk1/2 and pi3k signaling pathways.
Wilden, Peter A., Yehenew M. Agazie, Rebecca Kaufman, & Stephen P.
Halenda.
Department of Pharmacology, the Molecular Biology Program, and Food
for the 21st Century Nutrition Program, University of Missouri,
School of Medicine, Columbia, MO 65212
APStracts 5:0211H, 1998.
Vascular smooth muscle cells respond to the purinergic agonist ATP by
increasing intracellular calcium concentration and increasing the
rate of cell proliferation. In many cells the extracellular signal
regulated kinase (Erk) cascade plays an important role in cellular
proliferation. We have studied the effect of extracellular ATP on Erk
activation and cell proliferation. ATP binding to a UTP-sensitive P2Y
nucleotide receptor activates Erk1/2 in a time and dose dependent
manner in coronary artery smooth muscle cells (CASMC). ATP-induced
activation of Erk1/2 is dependent on the dual specificity kinase MEK,
but independent of the phosphatidylinositol 3-kinase (PI3K) activity.
We provide evidence that both Erk1/2 and PI3K activities are required
for CASMC proliferation. Thus, ATP-stimulated of CASMC proliferation
requires independent activation of both the Erk and PI3K signaling
pathways.
Received 26 November 1997; accepted in final form 12 May 1998.
APS Manuscript Number H1081-7.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 16 June 1998