Linked Life Data

20558612

Source:http://linkedlifedata.com/resource/pubmed/id/20558612

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-9-24
pubmed:abstractText
The adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a regulator of energy balance at the cellular and whole-body levels, but little is known about the role of AMPK in platelet activation. We report that both the ?1 and ?2 AMPK isoforms are expressed by human and murine platelets and that thrombin elicits the phosphorylation of AMPK? as well as the upstream kinase, liver kinase B1 (LKB1). In human platelets, the kinase inhibitors iodotubercidin and compound C significantly inhibited thrombin-induced platelet aggregation and clot retraction without affecting the initial increase in [Ca(2+)](i). Clot retraction was also impaired in platelets from AMPK?2(-/-) mice but not from wild-type littermates or AMPK?1(-/-) mice. Moreover, rebleeding was more frequent in AMPK?2(-/-) mice, and the FeCl(3)-induced thrombi formed in AMPK?2(-/-) mice were unstable. Mechanistically, AMPK?2 was found to phosphorylate in vitro the Src-family kinase, Fyn, and isoform deletion resulted in the attenuated threonine phosphorylation of Fyn as well as the subsequent tyrosine phosphorylation of its substrate, ?3 integrin. These data indicate that AMPK?2-by affecting Fyn phosphorylation and activity-plays a key role in platelet ?IIb?3 integrin signaling, leading to clot retraction and thrombus stability.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
23
pubmed:volume
116
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2134-40
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
AMPK ?2 subunit is involved in platelet signaling, clot retraction, and thrombus stability.
pubmed:affiliation
Institute for Vascular Signalling, Centre for Molecular Medicine, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't