Linked Life Data

8900143

Source:http://linkedlifedata.com/resource/pubmed/id/8900143

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
43
pubmed:dateCreated
1996-12-16
pubmed:abstractText
Although there are multiple potential collagen-binding proteins on platelets, the contribution of each to collagen-induced signaling events and platelet activation is unclear. We investigated which early platelet signaling events, if any, could be attributed specifically to the binding of collagen to one of its receptors, the alpha2beta1 integrin. Treatment of platelets with collagen induced a rapid activation of the non-receptor tyrosine kinase, Syk, as measured by an increase in phosphorylation and kinase activity. Collagen also induced the rapid phosphorylation of phospholipase Cgamma2 (PLCgamma2). The phosphorylation of both Syk and PLCgamma2, as well as platelet aggregation, was blocked by an anti-alpha2beta1 integrin monoclonal antibody (P1E6), demonstrating that collagen binding to alpha2beta1 is necessary for signaling. Cross-linking of the alpha2beta1 integrin with stimulatory monoclonal antibody against either the beta1 or alpha2 subunit stimulated the phosphorylation of both Syk and PLCgamma2. However, antibody stimulation was dependent on co-stimulation of the FcgammaII receptor (CD32) since specific F(ab')2 fragments did not induce Syk and PLCgamma2 phosphorylation. Thus, these results suggest that occupancy of alpha2beta1 by collagen is necessary, but that a co-receptor, in addition to alpha2beta1, is required for these collagen-induced signaling events. Moreover, the P1E6 antibody did not inhibit all collagen-induced tyrosine phosphorylation events, demonstrating that collagen also induces phosphorylation events that are independent of the alpha2beta1 integrin. In addition to Syk and PLCgamma2, we identified the FcgammaII receptor (FcgammaRII) as being rapidly phosphorylated in response to collagen stimulation, even in the absence of antibodies. Finally, to determine if Syk activation precedes and directly contributes to the phosphorylation of PLCgamma2, platelets were preincubated with the Syk-selective kinase inhibitor, piceatannol. A concentration of piceatannol that inhibited the phosphorylation and kinase activity of Syk, but had no effect on Src kinase activity, blocked the collagen-induced phosphorylation of PLCgamma2 and also inhibited collagen-induced platelet aggregation. Our results begin to delineate a signaling pathway whereby occupancy of the alpha2beta1 integrin is required, but not sufficient, for collagen-induced activation of Syk and the subsequent phosphorylation of PLCgamma2. These events are necessary for platelet activation and aggregation in response to collagen.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Collagen, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Precursors, http://linkedlifedata.com/resource/pubmed/chemical/Integrins, http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes, http://linkedlifedata.com/resource/pubmed/chemical/Phospholipase C gamma, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Collagen, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Fc, http://linkedlifedata.com/resource/pubmed/chemical/Syk kinase, http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases, http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
26668-76
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
The alpha2beta1 integrin is a necessary co-receptor for collagen-induced activation of Syk and the subsequent phosphorylation of phospholipase Cgamma2 in platelets.
pubmed:affiliation
Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.