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Am J Physiol Lung Cell Mol Physiol 281: L786-L798, 2001;
1040-0605/01 $5.00
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Vol. 281, Issue 4, L786-L798, October 2001

PDGF-BB-mediated activation of p42MAPK is independent of PDGF beta -receptor tyrosine phosphorylation

Nicholas J. Cartel1,2,*, Jason Liu1,*, Jinxia Wang1, and Martin Post1,2,3,4

1 Canadian Institutes of Health Research Group in Lung Development, Programme in Lung Biology, Research Institute, and 4 Department of Pediatrics, The Hospital for Sick Children, Toronto M5G 1X8; and Departments of 3 Physiology and 2 Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada M5S 1A1

Herein, we investigated the activity of mitogen-activated protein kinase (MAPK), a key component of downstream signaling events, which is activated subsequent to platelet-derived growth factor (PDGF)-BB stimulation. Specifically, p42MAPK activity peaked 60 min after addition of PDGF-BB, declined thereafter, and was determined not to be a direct or necessary component of glycosaminoglycan (GAG) synthesis. PDGF-BB also activated MAPK kinase 2 (MAPKK2) but had no effect on MAPKK1 and Raf-1 activity. Chemical inhibition of Janus kinase, phosphatidylinositol 3-kinase, Src kinase, or tyrosine phosphorylation inhibition of the PDGF beta -receptor (PDGFR-beta ) did not abrogate PDGF-BB-induced p42MAPK activation or its threonine or tyrosine phosphorylation. A dominant negative cytoplasmic receptor for hyaluronan-mediated motility variant 4 (RHAMMv4), a regulator of MAPKK-MAPK interaction and activation, did not inhibit PDGF-BB-induced p42MAPK activation nor did a construct expressing PDGFR-beta with cytoplasmic tyrosines mutated to phenylalanine. However, overexpression of a dominant negative PDGFR-beta lacking the cytoplasmic signaling domain abrogated p42MAPK activity. These results suggest that PDGF-BB-mediated activation of p42MAPK requires the PDGFR-beta but is independent of its tyrosine phosphorylation.

mitogen-activated protein kinase; platelet-derived growth factor receptor; fetal development; lung fibroblasts; tyrosine phosphorylation


* Nicholas J. Cartel and Jason Liu contributed equally to this work.




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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]




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