Source:http://linkedlifedata.com/resource/pubmed/id/12036880
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
2002-5-30
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pubmed:abstractText |
P-selectin glycoprotein ligand-1 (PSGL-1) serves as the leukocyte ligand for P-selectin, and many of the structural features of its ectodomain required for interactions with P-selectin have been uncovered. In contrast, the function of the highly conserved PSGL-1 cytoplasmic domain has not been explored. Stable transfectants expressing similar levels of either wild-type PSGL-1 or truncated PSGL-1 in which only 4 cytoplasmic residues were retained (designated PSGL-1 Delta cyto), were analyzed. Transfectants expressing full-length PSGL-1 rolled well on P-selectin. In contrast, rolling was almost completely absent in cells transfected with PSGL-1 Delta cyto, even at low shear. Importantly, cells expressing truncated PSGL-1 were able to bind soluble P-selectin and to bind COS cells overexpressing P-selectin, demonstrating that the P-selectin binding site on the PSGL-1 Delta cyto transfectants was intact and was capable of recognizing P-selectin. Impaired rolling by PSGL-1 Delta cyto transfectants was not due to alterations in subcellular localization because both wild-type and truncated PSGL-1 had similar surface distributions on K562 transfectants. Treatment of cells expressing native PSGL-1 with actin cytoskeletal toxins inhibited adhesion in a dose-dependent way. PSGL-1 was associated with the actin cytoskeleton, and this interaction was greatly impaired in PSGL-1 Delta cyto- expressing cells. The PSGL-1 cytoplasmic domain interacted selectively with the ezrin/radixin/moesin (ERM) protein moesin, but not with other ERM proteins or several other cytoskeletal linker proteins. Pharmacologic disruption of interactions between moesin and F-actin in cells expressing PSGL-1 resulted in a dose-dependent inhibition of rolling on P-selectin. Thus, attachment of PSGL-1 to the leukocyte cortical cytoskeleton is essential for leukocyte rolling on P-selectin.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Microfilament Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/P-Selectin,
http://linkedlifedata.com/resource/pubmed/chemical/P-selectin ligand protein,
http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine,
http://linkedlifedata.com/resource/pubmed/chemical/moesin
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0006-4971
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
99
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4494-502
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12036880-Actins,
pubmed-meshheading:12036880-Cell Line,
pubmed-meshheading:12036880-Cytoskeleton,
pubmed-meshheading:12036880-Humans,
pubmed-meshheading:12036880-Leukocytes,
pubmed-meshheading:12036880-Membrane Glycoproteins,
pubmed-meshheading:12036880-Microfilament Proteins,
pubmed-meshheading:12036880-Mutagenesis, Site-Directed,
pubmed-meshheading:12036880-P-Selectin,
pubmed-meshheading:12036880-Protein Binding,
pubmed-meshheading:12036880-Protein Structure, Tertiary,
pubmed-meshheading:12036880-Staurosporine,
pubmed-meshheading:12036880-Transfection
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pubmed:year |
2002
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pubmed:articleTitle |
Attachment of the PSGL-1 cytoplasmic domain to the actin cytoskeleton is essential for leukocyte rolling on P-selectin.
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pubmed:affiliation |
Department of Microbiology/Immunology, Northwestern University Medical School, Chicago, IL 60611, USA. krs133@northwestern.edu
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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