Linked Life Data

11264290

Source:http://linkedlifedata.com/resource/pubmed/id/11264290

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2001-5-30
pubmed:abstractText
When Glu-plasminogen is bound to cells, plasmin (Pm) formation by plasminogen (Pg) activators is markedly enhanced compared with the reaction in solution. It is not known whether the direct activation of Glu-Pg by Pg activators is promoted on the cell surface or whether plasminolytic conversion of Glu-Pg to the more readily activated Lys-Pg is necessary for enhanced Pm formation on the cell surface. To distinguish between these potential mechanisms, we tested whether Pm formation on the cell surface could be stimulated in the absence of conversion of Glu-Pg to Lys-Pg. Rates of activation of Glu-Pg, Lys-Pg, and a mutant Glu-Pg, [D646E]Glu-Pg, by either tissue Pg activator (t-PA) or urokinase (u-PA) were compared when these Pg forms were either bound to human umbilical vein endothelial cells (HUVEC) or in solution. ([D646E]Glu-Pg can be cleaved at the Arg(561)-Val(562) bond by Pg activators but does not possess Pm activity subsequent to this cleavage because of the mutation of Asp(646) of the serine protease catalytic triad.) Glu-Pg activation by t-PA was enhanced on HUVEC compared with the solution phase by 13-fold. In contrast, much less enhancement of Pg activation was observed with [D646E]Glu-Pg ( approximately 2-fold). Although the extent of activation of Lys-Pg on cells was similar to that of Glu-Pg, the cells afforded minimal enhancement of Lys-Pg activation compared with the solution phase (1.3-fold). Similar results were obtained when u-PA was used as activator. When Glu-Pg was bound to the cell in the presence of either t-PA or u-PA, conversion to Lys-Pg was observed, but conversion of ([D646E]Glu-Pg to ([D646E]Lys-Pg was not detected, consistent with the conversion of Glu-Pg to Lys-Pg being necessary for optimal enhancement of Pg activation on cell surfaces. Furthermore, we found that conversion of [D646E]Glu-Pg to [D646E]Lys-Pg by exogenous Pm was markedly enhanced ( approximately 20-fold) on the HUVEC surface, suggesting that the stimulation of the conversion of Glu-Pg to Lys-Pg is a key mechanism by which cells enhance Pg activation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
19078-83
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11264290-Cell Membrane, pubmed-meshheading:11264290-Cell Movement, pubmed-meshheading:11264290-Cells, Cultured, pubmed-meshheading:11264290-Dose-Response Relationship, Drug, pubmed-meshheading:11264290-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:11264290-Endothelium, Vascular, pubmed-meshheading:11264290-Fibrinolytic Agents, pubmed-meshheading:11264290-Humans, pubmed-meshheading:11264290-Mutation, pubmed-meshheading:11264290-Peptide Fragments, pubmed-meshheading:11264290-Plasminogen, pubmed-meshheading:11264290-Plasminogen Activators, pubmed-meshheading:11264290-Protein Binding, pubmed-meshheading:11264290-Serine Endopeptidases, pubmed-meshheading:11264290-Time Factors, pubmed-meshheading:11264290-Tissue Plasminogen Activator, pubmed-meshheading:11264290-Umbilical Cord, pubmed-meshheading:11264290-Urokinase-Type Plasminogen Activator
pubmed:year
2001
pubmed:articleTitle
Conversion of Glu-plasminogen to Lys-plasminogen is necessary for optimal stimulation of plasminogen activation on the endothelial cell surface.
pubmed:affiliation
Scripps Research Institute, La Jolla, California 92037, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't