Signal Transduction in Smooth Muscle. Invited Review: The circle of life: cell cycle
regulation in airway smooth muscle.
Ammit, Alaina J., and Reynold A. Panettieri, Jr.
1Respiratory Research Group, Faculty of Pharmacy, University of Sydney, New
South Wales 2006, Australia; and 2Pulmonary, Allergy and Critical Care Division,
Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
19104«hyphen»6160
APStracts 8:0303A, 2001.
Severe asthma is characterized by increased airway smooth muscle (ASM) mass, due
predominantly to ASM hyperplasia. Diverse stimuli, which include growth factors,
plasma- or inflammatory cell-derived mediators, contractile agonists, cytokines, and
extracellular matrix proteins, induce ASM proliferation. Mitogens act via receptor
tyrosine kinase, G protein-coupled receptors, or cytokine receptors, to activate p21ras and
stimulate two parallel signaling pathways in ASM cells, namely, the extracellular signal-
regulated kinase (ERK) or the phosphatidylinositol 3-kinase (PI3K) pathways. ERK and
PI3K regulate cell cycle protein expression and thus modulate cell cycle traversal. ERK
activation and downstream effectors of PI3K, such as Rac1 and Cdc42, stimulate
expression of cyclin D1, a key regulator of G1 progression in the mammalian cell cycle.
In addition, PI3K activates 70-kDa ribosomal S6 kinase, an enzyme that also regulates
the translation of many cell cycle proteins, including the elongation factor E2F. The
present review examines the mitogens and critical signal transduction pathways that
stimulate ASM cell proliferation. Further study in this area may reveal new therapeutic
targets to abrogate ASM hyperplasia in diseases such as asthma and chronic obstructive
pulmonary disease.
APS Manuscript Number A0352-1.
Article publication pending J Appl Physiol
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 18 June 2001