Linked Life Data

8530514

Source:http://linkedlifedata.com/resource/pubmed/id/8530514

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
51
pubmed:dateCreated
1996-1-30
pubmed:abstractText
Cellular response to platelet-derived growth factor AA (PDGF-AA) is mediated exclusively by the PDGF alpha-receptor. Vascular smooth muscle cells (VSMCs) in culture typically express very low levels of alpha-receptor. In this study, we demonstrate that the proteinase inhibitor and cytokine carrier alpha 2-macroglobulin (alpha 2M) increases rat VSMC PDGF alpha-receptor expression. PDGF alpha-receptor mRNA levels increased 3-fold by 6 h and were sustained at that level through 24 h in VSMCs treated with 280 nM methylamine-modified alpha 2M (alpha 2M-MA), a form of activated alpha 2M. PDGF beta-receptor mRNA levels were unchanged in the same time period. In 125I-PDGF-AA binding experiments, treatment of VSMCs with alpha 2M-MA increased the maximum binding capacity (Bmax) from 1.9 to 9.2 fmol/mg of cell protein without affecting binding affinity (KD approximately 80 pM). alpha 2M-MA also increased the VSMC response to PDGF-AA as determined by tyrosine phosphorylation of a 170-kDa band, corresponding in mass to the PDGF alpha-receptor. The native form of alpha 2M was comparable to alpha 2M-MA in its ability to increase PDGF-AA binding to VSMCs and tyrosine phosphorylation of the 170-kDa band. Recombinant and proteolytic alpha 2M derivatives were used to demonstrate that alpha 2M increases PDGF alpha-receptor expression by binding VSMC-secreted cytokine(s) and interrupting an autocrine loop that ordinarily suppresses alpha-receptor expression in these cells. Transforming growth factor-beta-neutralizing antibody mimicked the activity of alpha 2M, increasing the binding capacity of VSMCs for PDGF-AA. This study demonstrates that VSMC PDGF alpha-receptor expression and responsiveness to PDGF-AA are regulated by autocrine transforming growth factor-beta activity, potentially other autocrine growth factors, and alpha 2M.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
30741-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:8530514-Animals, pubmed-meshheading:8530514-Aorta, pubmed-meshheading:8530514-Cell Division, pubmed-meshheading:8530514-Cells, Cultured, pubmed-meshheading:8530514-DNA, pubmed-meshheading:8530514-Fibroblast Growth Factor 2, pubmed-meshheading:8530514-Gene Expression, pubmed-meshheading:8530514-Humans, pubmed-meshheading:8530514-Kinetics, pubmed-meshheading:8530514-Muscle, Smooth, Vascular, pubmed-meshheading:8530514-Platelet-Derived Growth Factor, pubmed-meshheading:8530514-RNA, Messenger, pubmed-meshheading:8530514-Rats, pubmed-meshheading:8530514-Rats, Sprague-Dawley, pubmed-meshheading:8530514-Receptor, Platelet-Derived Growth Factor alpha, pubmed-meshheading:8530514-Receptors, Platelet-Derived Growth Factor, pubmed-meshheading:8530514-Structure-Activity Relationship, pubmed-meshheading:8530514-Up-Regulation, pubmed-meshheading:8530514-alpha-Macroglobulins
pubmed:year
1995
pubmed:articleTitle
Native and activated forms of alpha 2-macroglobulin increase expression of platelet-derived growth factor alpha-receptor in vascular smooth muscle cells. Evidence for autocrine transforming growth factor-beta activity.
pubmed:affiliation
Department of Biochemistry, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.