AJP - Lung Journal of Applied Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Lung Cell Mol Physiol 274: L702-L713, 1998;
1040-0605/98 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Liu, J.
Right arrow Articles by Post, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liu, J.
Right arrow Articles by Post, M.
Vol. 274, Issue 5, L702-L713, May 1998

PDGF-induced glycosaminoglycan synthesis is mediated via phosphatidylinositol 3-kinase

Jason Liu, Dora Fitzli, Mingyao Liu, Irene Tseu, Isabella Caniggia, Daniela Rotin, and Martin Post

Medical Research Council Group in Lung Development and Lung Biology Program, Department of Pediatrics, Hospital for Sick Children Research Institute, University of Toronto, Toronto, Ontario, Canada M5G 1X8

Platelet-derived growth factor (PDGF)-BB has been shown previously to increase glycosaminoglycan (GAG) synthesis but not DNA synthesis in freshly isolated fetal lung fibroblasts. In the present study, we found that PDGF-BB also enhanced 35SO4 incorporation into the small, soluble proteoglycan biglycan without affecting biglycan's core protein mRNA expression, suggesting that PDGF-BB mainly affects GAG chain elongation and/or sulfation. PDGF-BB-stimulated GAG synthesis was abrogated by tyrphostin 9, a PDGF receptor-associated tyrosine kinase inhibitor, implying that the stimulatory effect is mediated via the PDGF beta -receptor (PDGFR). The intracellular signal transduction pathways that mediate PDGF-BB-stimulated GAG synthesis in fetal lung fibroblasts were investigated. On ligand-induced tyrosine phosphorylation, PDGFR associated with phospholipase C (PLC)-gamma 1, Ras GTPase activating protein (RasGAP), and phosphatidylinositol 3-kinase (PI3K) but not with the Syp-growth factor receptor-bound protein 2-Son of Sevenless complex. Association of PDGFR with PLC-gamma 1 and RasGAP followed by their tyrosine phosphorylation failed, however, to activate PLC-gamma 1, protein kinase C (PKC), and Ras. Neither a PLC-gamma inhibitor, U-73122; a PKC inhibitor, calphostin C; nor a mitogen-activated protein kinase kinase inhibitor, PD-98059, inhibited PDGF-BB-induced GAG synthesis. In contrast, PDGF-BB stimulation triggered PDGFR-associated PI3K activity. Both PDGF-BB-induced PI3K activation and GAG synthesis were abolished by the PI3K inhibitors wortmannin and LY-294002. The results suggest that PI3K is a downstream mediator of PDGF-BB-stimulated GAG synthesis in fetal rat lung fibroblasts.

platelet-derived growth factor; deoxyribonucleic acid synthesis; fetal lung fibroblasts


This article has been cited by other articles:


Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
N. J. Cartel and M. Post
Abrogation of apoptosis through PDGF-BB-induced sulfated glycosaminoglycan synthesis and secretion
Am J Physiol Lung Cell Mol Physiol, February 1, 2005; 288(2): L285 - L293.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
R. N. N. Han, M. Post, A. K. Tanswell, and S. J. Lye
Insulin-Like Growth Factor-I Receptor-Mediated Vasculogenesis/Angiogenesis in Human Lung Development
Am. J. Respir. Cell Mol. Biol., February 1, 2003; 28(2): 159 - 169.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
N. J. Cartel, J. Liu, J. Wang, and M. Post
PDGF-BB-mediated activation of p42MAPK is independent of PDGF {beta}-receptor tyrosine phosphorylation
Am J Physiol Lung Cell Mol Physiol, October 1, 2001; 281(4): L786 - L798.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
R. Koslowski, U. Pfeil, H. Fehrenbach, M. Kasper, E. Skutelsky, and K-W. Wenzel
Changes in xylosyltransferase activity and in proteoglycan deposition in bleomycin-induced lung injury in rat
Eur. Respir. J., August 1, 2001; 18(2): 347 - 356.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M. Liu, A. K. Tanswell, and M. Post
Mechanical force-induced signal transduction in lung cells
Am J Physiol Lung Cell Mol Physiol, October 1, 1999; 277(4): L667 - L683.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online