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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
1999-2-16
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pubmed:abstractText |
Protein seryl/threonyl phosphatase inhibitors such as calyculin A block inside-out and outside-in platelet signaling. Our studies demonstrate that the addition of calyculin A blocks platelet adhesion and spreading on fibrinogen, responses that depend on integrin alphaIIb beta3 signaling. We hypothesized that this reflects a change in alphaIIb beta3 structure caused by a specific state of phosphorylation. We show that addition of calyculin A leads to increased phosphorylation of the beta3 subunit, and phosphoamino acid analysis reveals that only threonine residues become phosphorylated; sequence analysis by Edman degradation established that threonine 753 became stoichiometrically phosphorylated during inhibition of platelet phosphatases by calyculin A. This region of beta3 is linked to outside-in signaling such as platelet spreading responses. The effect of calyculin A on platelet adhesion and spreading and on the phosphorylation of T-753 in beta3 is reversed by the calcium ionophore A23187, demonstrating that these effects of calyculin A are not generally toxic ones. We propose that phosphorylation of beta3 on threonine 753, a region of beta3 linked to outside-in signaling, may be a mechanism by which integrin alphaIIb beta3 function is regulated.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
22
|
pubmed:volume |
274
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1914-9
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9890945-Blood Platelets,
pubmed-meshheading:9890945-Cell Adhesion,
pubmed-meshheading:9890945-Cytoplasm,
pubmed-meshheading:9890945-Humans,
pubmed-meshheading:9890945-Oxazoles,
pubmed-meshheading:9890945-Phosphorylation,
pubmed-meshheading:9890945-Platelet Glycoprotein GPIIb-IIIa Complex,
pubmed-meshheading:9890945-Signal Transduction,
pubmed-meshheading:9890945-Threonine
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pubmed:year |
1999
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pubmed:articleTitle |
Phosphorylation sites in the integrin beta3 cytoplasmic domain in intact platelets.
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pubmed:affiliation |
Department of Cell Biology and Anatomy, New York Medical College, Valhalla, New York 10595, USA. ken_lerea@nymc.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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