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-receptor tyrosine phosphorylation
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
-receptor (PDGFR-
) 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-
with cytoplasmic tyrosines mutated to
phenylalanine. However, overexpression of a dominant negative PDGFR-
lacking the cytoplasmic signaling domain abrogated p42MAPK
activity. These results suggest that PDGF-BB-mediated activation of
p42MAPK requires the PDGFR-
but is independent of its
tyrosine phosphorylation.
mitogen-activated protein kinase; platelet-derived growth factor receptor; fetal development; lung fibroblasts; tyrosine phosphorylation
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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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