| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of 1 Pharmacology and 2 Pathology, University of Sydney, New South Wales 2006, Australia
Asthmatic airways are characterized by an increase in smooth muscle mass, due mainly to hyperplasia. Many studies suggest that extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2, respectively), one group of the mitogen-activated protein (MAP) kinase superfamily, play a key role in the signal transduction pathway leading to cell proliferation. PGE2 and forskolin inhibited mitogen-induced ERK activation. Inhibition of MAP kinase kinases 1 and 2 (MEK1 and MEK2, respectively), which are upstream from ERK, with the specific MEK inhibitor U-0126 blocked both cell proliferation and ERK activation. In addition, U-0126 inhibited mitogen-induced activation of p90 ribosomal S6 kinase and expression of c-Fos and cyclin D1, all of which are downstream from ERK in the signaling cascade that leads to cell proliferation. Antisense oligodeoxynucleotides directed to ERK1 and -2 mRNAs reduced ERK protein and cell proliferation. These results indicate that ERK is required for human airway smooth muscle cell proliferation. Thus targeting the control of ERK activation may provide a new therapeutic approach for hyperplasia seen in asthma.
asthma; antisense extracellular signal-regulated kinase; p90 ribosomal S6 kinase; c-Fos; cyclin D1
This article has been cited by other articles:
|
|
 |
|
  K. M. Kassel, T. A. Wyatt, R. A. Panettieri Jr., and M. L. Toews Inhibition of human airway smooth muscle cell proliferation by 2-adrenergic receptors and cAMP is PKA independent: evidence for EPAC involvement Am J Physiol Lung Cell Mol Physiol, January 1, 2008; 294(1): L131 - L138. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Osawa, P. D. Yim, D. Xu, R. A. Panettieri, and C. W. Emala Raf-1 kinase mediates adenylyl cyclase sensitization by TNF-{alpha} in human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, June 1, 2007; 292(6): L1414 - L1421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. R. A. Johnson, J. K. Burgess, Q. Ge, M. Poniris, S. Boustany, S. M. Twigg, and J. L. Black Connective Tissue Growth Factor Induces Extracellular Matrix in Asthmatic Airway Smooth Muscle Am. J. Respir. Crit. Care Med., January 1, 2006; 173(1): 32 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. A. Marganski, S. S. Gangopadhyay, H.-D. Je, C. Gallant, and K. G. Morgan Targeting of a Novel Ca+2/Calmodulin-Dependent Protein Kinase II Is Essential for Extracellular Signal-Regulated Kinase-Mediated Signaling in Differentiated Smooth Muscle Cells Circ. Res., September 16, 2005; 97(6): 541 - 549. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Citro, S. Ravasi, G. E. Rovati, and V. Capra Thromboxane Prostanoid Receptor Signals Through Gi Protein to Rapidly Activate Extracellular Signal-Regulated Kinase in Human Airways Am. J. Respir. Cell Mol. Biol., April 1, 2005; 32(4): 326 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Halayko, S. Kartha, G. L. Stelmack, J. McConville, J. Tam, B. Camoretti-Mercado, S. M. Forsythe, M. B. Hershenson, and J. Solway Phophatidylinositol-3 Kinase/Mammalian Target of Rapamycin/p70S6K Regulates Contractile Protein Accumulation in Airway Myocyte Differentiation Am. J. Respir. Cell Mol. Biol., September 1, 2004; 31(3): 266 - 275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hjoberg, L. Le, A. Imrich, V. Subramaniam, S. I. Mathew, J. Vallone, K. J. Haley, F. H. Y. Green, S. A. Shore, and E. S. Silverman Induction of early growth-response factor 1 by platelet-derived growth factor in human airway smooth muscle Am J Physiol Lung Cell Mol Physiol, April 1, 2004; 286(4): L817 - L825. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Nabeyrat, G. E. Jones, P. S. Fenwick, P. J. Barnes, and L. E. Donnelly Mitogen-activated protein kinases mediate peroxynitrite-induced cell death in human bronchial epithelial cells Am J Physiol Lung Cell Mol Physiol, June 1, 2003; 284(6): L1112 - L1120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Page, J. Li, K. C. Corbit, K. M. Rumilla, J.-W. Soh, I. B. Weinstein, C. Albanese, R. G. Pestell, M. R. Rosner, and M. B. Hershenson Regulation of Airway Smooth Muscle Cyclin D1 Transcription by Protein Kinase C-{delta} Am. J. Respir. Cell Mol. Biol., August 1, 2002; 27(2): 204 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-y. Wang, J. Kanungo, and C. C. Malbon Expression of Galpha 13 (Q226L) Induces P19 Stem Cells to Primitive Endoderm via MEKK1, 2, or 4 J. Biol. Chem., January 25, 2002; 277(5): 3530 - 3536. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Wu, H.-W. Shen, T.-F. Wu, L. F. Brass, and K.-C. Sung Extracellular Signal-Regulated Kinases and G Protein-Coupled Receptors in Megakaryocytic Human Erythroleukemia Cells: Selective Activation, Differential Regulation, and Dissociation from Mitogenesis J. Pharmacol. Exp. Ther., January 1, 2002; 300(1): 339 - 345. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Ammit and R. A. Panettieri Jr. Signal Transduction in Smooth Muscle: Invited Review: The circle of life: cell cycle regulation in airway smooth muscle J Appl Physiol, September 1, 2001; 91(3): 1431 - 1437. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
