Document Detail


PDGF-BB-mediated activation of p42(MAPK) is independent of PDGF beta-receptor tyrosine phosphorylation.
MedLine Citation:
PMID:  11557582     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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, p42(MAPK) 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 p42(MAPK) 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 p42(MAPK) 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 p42(MAPK) activity. These results suggest that PDGF-BB-mediated activation of p42(MAPK) requires the PDGFR-beta but is independent of its tyrosine phosphorylation.
Authors:
N J Cartel; J Liu; J Wang; M Post
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  281     ISSN:  1040-0605     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2001-09-14     Completed Date:  2001-10-18     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L786-98     Citation Subset:  IM    
Affiliation:
Canadian Institutes of Health Research Group in Lung Development, Programme in Lung Biology, Research Institute, Toronto, Ontario, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anticoagulants / pharmacology*
Benzoquinones
Cells, Cultured
Enzyme Activation / drug effects
Enzyme Inhibitors / pharmacology
Female
Fibroblasts / cytology,  enzymology
Lactams, Macrocyclic
Lung / cytology,  embryology,  metabolism
MAP Kinase Kinase 2
MAP Kinase Signaling System / drug effects,  physiology
Male
Mitogen-Activated Protein Kinase 1 / metabolism*
Mitogen-Activated Protein Kinase Kinases / metabolism
Mutagenesis / physiology
Phosphorylation
Platelet-Derived Growth Factor / pharmacology*
Protein-Tyrosine Kinases / metabolism
Proto-Oncogene Proteins c-raf / metabolism
Quinones / pharmacology
Rats
Rats, Wistar
Receptor, Platelet-Derived Growth Factor beta / genetics,  metabolism*
Threonine / metabolism
Transfection
Tyrosine / metabolism
Tyrphostins / pharmacology
Chemical
Reg. No./Substance:
0/Anticoagulants; 0/Benzoquinones; 0/Enzyme Inhibitors; 0/Lactams, Macrocyclic; 0/Platelet-Derived Growth Factor; 0/Quinones; 0/Tyrphostins; 0/platelet-derived growth factor BB; 55520-40-6/Tyrosine; 70563-58-5/herbimycin; 71308-35-5/tyrphostin AG17; 72-19-5/Threonine; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.1/Receptor, Platelet-Derived Growth Factor beta; EC 2.7.11.1/Proto-Oncogene Proteins c-raf; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.12.2/MAP Kinase Kinase 2; EC 2.7.12.2/Mitogen-Activated Protein Kinase Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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