Linked Life Data

14525764

Source:http://linkedlifedata.com/resource/pubmed/id/14525764

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-1-19
pubmed:abstractText
The mechanisms by which agonists activate glycoprotein (GP) IIb-IIIa function remain unclear. We have reported data on a patient with thrombocytopenia and impaired receptor-mediated aggregation, phosphorylation of pleckstrin (a protein kinase C [PKC] substrate), and activation of the GPIIb-IIIa complex. Abnormalities in hematopoietic transcription factors have been associated with thrombocytopenia and platelet dysfunction. To define the molecular mechanisms, we amplified from patient platelet RNA exons 3 to 6 of core-binding factor A2 (CBFA2) cDNA, which encompasses the DNA-binding Runt domain; a 13-nucleotide (nt) deletion was found (796-808 nt). The gDNA revealed a heterozygous mutation (G>T) in intron 3 at the splice acceptor site for exon 4, leading to a frameshift with premature termination in the Runt domain. On immunoblotting, platelet CBFA2, PKC-, albumin, and IgG were decreased, but pleckstrin, PKC-alpha, -betaI, -betaII, -eta, -epsilon, -delta, and -zeta, and fibrinogen were normal. Our conclusions are that (1) CBFA2 mutation is associated with not only thrombocytopenia, but also impaired platelet protein phosphorylation and GPIIb-IIIa activation; (2) proteins regulated by CBFA2 are required for inside-out signal transduction-dependent activation of GPIIb-IIIa; and (3) we have documented the first deficiency of a human PKC isozyme (PKC-), suggesting a major role of this isozyme in platelet production and function.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
948-54
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:14525764-Amino Acid Sequence, pubmed-meshheading:14525764-Base Sequence, pubmed-meshheading:14525764-Blood Platelets, pubmed-meshheading:14525764-Blood Proteins, pubmed-meshheading:14525764-DNA, Complementary, pubmed-meshheading:14525764-Female, pubmed-meshheading:14525764-Frameshift Mutation, pubmed-meshheading:14525764-Heterozygote, pubmed-meshheading:14525764-Humans, pubmed-meshheading:14525764-Isoenzymes, pubmed-meshheading:14525764-Male, pubmed-meshheading:14525764-Molecular Sequence Data, pubmed-meshheading:14525764-Mutation, pubmed-meshheading:14525764-Phosphoproteins, pubmed-meshheading:14525764-Phosphorylation, pubmed-meshheading:14525764-Platelet Glycoprotein GPIIb-IIIa Complex, pubmed-meshheading:14525764-Protein Kinase C, pubmed-meshheading:14525764-RNA, Messenger, pubmed-meshheading:14525764-Signal Transduction, pubmed-meshheading:14525764-Thrombocytopenia
pubmed:year
2004
pubmed:articleTitle
Association of CBFA2 mutation with decreased platelet PKC-theta and impaired receptor-mediated activation of GPIIb-IIIa and pleckstrin phosphorylation: proteins regulated by CBFA2 play a role in GPIIb-IIIa activation.
pubmed:affiliation
Division of Hematology and Thromboembolic Diseases, Temple University School of Medicine, 3400 N Broad St, OMS 300, Philadelphia, PA 19140, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't