|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
21
|
|
pubmed:dateCreated |
1996-12-4
|
|
pubmed:abstractText |
Integrins are major two-way signaling receptors responsible for the attachment of cells to the extracellular matrix and for cell-cell interactions that underlie immune responses, tumor metastasis, and progression of atherosclerosis and thrombosis. We report the structure-function analysis of the cytoplasmic tail of integrin beta 3 (glycoprotein IIla) based on the cellular import of synthetic peptide analogs of this region. Among the four overlapping cell-permeable peptides, only the peptide carrying residues 747-762 of the carboxyl-terminal segment of integrin beta 3 inhibited adhesion of human erythroleukemia (HEL) cells and of human endothelial cells (ECV) 304 to immobilized fibrinogen mediated by integrin beta 3 heterodimers, alpha IIb beta 3, and alpha v beta 3, respectively. Inhibition of adhesion was integrin-specific because the cell-permeable beta 3 peptide (residues 747-762) did not inhibit adhesion of human fibroblasts mediated by integrin beta 1 heterodimers. Conversely, a cell-permeable peptide representing homologous portion of the integrin beta 1 cytoplasmic tail (residues 788-803) inhibited adhesion of human fibroblasts, whereas it was without effect on adhesion of HEL or ECV 304 cells. The cell-permeable integrin beta 3 peptide (residues 747-762) carrying a known loss-of-function mutation (Ser752Pro) responsible for the genetic disorder Glanzmann thrombasthenia Paris I did not inhibit cell adhesion of HEL or ECV 304 cells, whereas the beta 3 peptide carrying a Ser752Ala mutation was inhibitory. Although Ser752 is not essential, Tyr747 and Tyr759 form a functionally active tandem because conservative mutations Tyr747Phe or Tyr759Phe resulted in a nonfunctional cell permeable integrin beta 3 peptide. We propose that the carboxyl-terminal segment of the integrin beta 3 cytoplasmic tail spanning residues 747-762 constitutes a major intracellular cell adhesion regulatory domain (CARD) that modulates the interaction of integrin beta 3-expressing cells with immobilized fibrinogen. Import of cell-permeable peptides carrying this domain results in inhibition "from within" of the adhesive function of these integrins.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-1339660,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-1376731,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-1435324,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-1435325,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-1438206,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-1555235,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-1690702,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-1709375,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-1908469,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-1948065,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-1968060,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-1985087,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-2078570,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-2439501,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-2501308,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-3494014,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-6201359,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-7528772,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-7545337,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-7592818,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-7593198,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-7652584,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-7694604,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-7721755,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-7782278,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-8314843,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-8636068,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8876221-944704
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Oct
|
|
pubmed:issn |
0027-8424
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
15
|
|
pubmed:volume |
93
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
11819-24
|
|
pubmed:dateRevised |
2011-3-28
|
|
pubmed:meshHeading |
pubmed-meshheading:8876221-Amino Acid Sequence,
pubmed-meshheading:8876221-Antigens, CD,
pubmed-meshheading:8876221-Antigens, CD29,
pubmed-meshheading:8876221-Biological Transport,
pubmed-meshheading:8876221-Cell Adhesion,
pubmed-meshheading:8876221-Cell Line,
pubmed-meshheading:8876221-Endothelium, Vascular,
pubmed-meshheading:8876221-Humans,
pubmed-meshheading:8876221-Integrin beta3,
pubmed-meshheading:8876221-Leukemia, Erythroblastic, Acute,
pubmed-meshheading:8876221-Male,
pubmed-meshheading:8876221-Molecular Sequence Data,
pubmed-meshheading:8876221-Peptide Fragments,
pubmed-meshheading:8876221-Peptides,
pubmed-meshheading:8876221-Platelet Membrane Glycoproteins,
pubmed-meshheading:8876221-Skin,
pubmed-meshheading:8876221-Tumor Cells, Cultured
|
|
pubmed:year |
1996
|
|
pubmed:articleTitle |
Identification of a functionally important sequence in the cytoplasmic tail of integrin beta 3 by using cell-permeable peptide analogs.
|
|
pubmed:affiliation |
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
