|
|
||||||||
Department of Pediatrics, University of Chicago, Chicago, Illinois 60637-1470
We have demonstrated that platelet-derived
growth factor (PDGF) stimulates p38 mitogen-activated protein (MAP)
kinase activation in bovine tracheal myocytes, suggesting that p38 is
involved in growth regulation. We therefore examined whether p38
regulates expression of cyclin D1, a G1 cyclin required for
cell cycle traversal. The chemical p38 inhibitors SB-202190 and
SB-203580 each increased basal and PDGF-induced cyclin D1 promoter
activity and protein abundance. Overexpression of a dominant negative
allele of MAP kinase kinase-3 (MKK3), an upstream activator of p38
,
had similar effects. Conversely, active MKK3 and MKK6, both of which
increase p38
activity, each decreased transcription from the cyclin
D1 promoter. Together, these data demonstrate that p38 negatively regulates cyclin D1 expression. We tested whether p38 regulates cyclin
D1 expression via inhibition of extracellular signal-regulated kinase
(ERK) activation. Chemical inhibitors of p38 induced modest ERK
phosphorylation and activation. However, dominant negative MKK3 was
insufficient to activate ERK, and active MKK3 and MKK6 did not
attenuate platelet-derived growth factor-mediated ERK activation. These
data are consistent with the notion that p38
negatively regulates
cyclin D1 expression via an ERK-independent pathway.
bovine; extracellular signal-regulated kinase; platelet-derived growth factor; signal transduction; mitogen-activated protein kinase
This article has been cited by other articles:
![]() |
S. Xie, M. B. Sukkar, R. Issa, N. M. Khorasani, and K. F. Chung Mechanisms of induction of airway smooth muscle hyperplasia by transforming growth factor-beta Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L245 - L253. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Zhang, S. Murakami, F. Coustry, Y. Wang, and B. de Crombrugghe Constitutive activation of MKK6 in chondrocytes of transgenic mice inhibits proliferation and delays endochondral bone formation PNAS, January 10, 2006; 103(2): 365 - 370. [Abstract] [Full Text] [PDF] |
||||
![]() |
S.-E. Chen, E. Gerken, Y. Zhang, M. Zhan, R. K. Mohan, A. S. Li, M. B. Reid, and Y.-P. Li Role of TNF-{alpha} signaling in regeneration of cardiotoxin-injured muscle Am J Physiol Cell Physiol, November 1, 2005; 289(5): C1179 - C1187. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. R. White, R. Tse, and B. A. Marroquin Stress-Activated Protein Kinases Mediate Cell Migration in Human Airway Epithelial Cells Am. J. Respir. Cell Mol. Biol., April 1, 2005; 32(4): 301 - 310. [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] |
||||
![]() |
L. Zhang, S. Pelech, and V.-J. Uitto Long-Term Effect of Heat Shock Protein 60 from Actinobacillus actinomycetemcomitans on Epithelial Cell Viability and Mitogen-Activated Protein Kinases Infect. Immun., January 1, 2004; 72(1): 38 - 45. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Amrani, O. Tliba, D. Choubey, C.-D. Huang, V. P. Krymskaya, A. Eszterhas, A. L. Lazaar, and R. A. Panettieri Jr. IFN-gamma inhibits human airway smooth muscle cell proliferation by modulating the E2F-1/Rb pathway Am J Physiol Lung Cell Mol Physiol, June 1, 2003; 284(6): L1063 - L1071. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Li, X. D. Johnson, S. Iazvovskaia, A. Tan, A. Lin, and M. B. Hershenson Signaling intermediates required for NF-kappa B activation and IL-8 expression in CF bronchial epithelial cells Am J Physiol Lung Cell Mol Physiol, February 1, 2003; 284(2): L307 - L315. [Abstract] [Full Text] [PDF] |
||||
![]() |
M.-C. Michoud, G. Napolitano, K. Maghni, V. Govindaraju, A. Cogo, and J. G. Martin Effects of Extracellular Triphosphate Nucleotides and Nucleosides on Airway Smooth Muscle Cell Proliferation Am. J. Respir. Cell Mol. Biol., December 1, 2002; 27(6): 732 - 738. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. B. Rice, J. L. Ingram, and J. C. Bonner p38 Mitogen-Activated Protein Kinase Regulates Growth Factor-Induced Mitogenesis of Rat Pulmonary Myofibroblasts Am. J. Respir. Cell Mol. Biol., December 1, 2002; 27(6): 759 - 765. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. P. Bauerfeld, M. B. Hershenson, and K. Page Cdc42, but not RhoA, regulates cyclin D1 expression in bovine tracheal myocytes Am J Physiol Lung Cell Mol Physiol, May 1, 2001; 280(5): L974 - L982. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Glassford, M. Holman, L. Banerji, E. Clayton, G. G. B. Klaus, M. Turner, and E. W.-F. Lam Vav Is Required for Cyclin D2 Induction and Proliferation of Mouse B Lymphocytes Activated via the Antigen Receptor J. Biol. Chem., October 26, 2001; 276(44): 41040 - 41048. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |