rdf:type |
|
lifeskim:mentions |
umls-concept:C0007634,
umls-concept:C0023516,
umls-concept:C0030685,
umls-concept:C0125090,
umls-concept:C0300500,
umls-concept:C0391871,
umls-concept:C0678594,
umls-concept:C0680255,
umls-concept:C0699040,
umls-concept:C0851285,
umls-concept:C1283071,
umls-concept:C1335808,
umls-concept:C1514873,
umls-concept:C1963578
|
pubmed:issue |
2
|
pubmed:dateCreated |
1995-9-7
|
pubmed:abstractText |
L-selectin mediates leukocyte rolling on vascular endothelium at sites of inflammation and lymphocyte migration to peripheral lymph nodes. L-selectin is rapidly shed from the cell surface after leukocyte activation by a proteolytic mechanism that cleaves the receptor in a membrane proximal extracellular region. This process may allow rapid leukocyte detachment from the endothelial surface before entry into tissues. In this study, the structural requirements for regulation of human L-selectin endoproteolytic release were examined through analysis of chimeric selectin molecules and mutant L-selectin receptors. The use of chimeric selectins and a cytoplasmic tail truncation mutant demonstrated that the extracellular membrane-proximal 15-amino acid region of L-selectin is required for endoproteolytic release. The introduction of alanine-scanning mutations within this membrane-proximal region did not prevent endoproteolytic release, indicating that a specific amino acid motif was not an absolute requirement for cleavage. Furthermore, alterations within the putative primary cleavage site (K283-S284) resulted in either constitutive endoproteolytic release of the receptor or inhibition of cell activation-induced shedding to variable extents. The length of the membrane-proximal region was also critical since truncations of this region completely abolished endoproteolytic release. Thus, release of L-selectin is likely to be regulated by the generation of an appropriate tertiary conformation within the membrane-proximal region of the receptor which allows recognition by a membrane-bound endoprotease with relaxed sequence specificity that cleaves the receptor at a specific distance from the plasma membrane. These observations suggest a generalized protein-processing pathway involved in the endoproteolytic release of specific transmembrane proteins which harbor widely differing primary sequences at or neighboring their cleavage sites.
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pubmed:grant |
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pubmed:commentsCorrections |
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http://linkedlifedata.com/resource/pubmed/commentcorrection/7543141-8424174
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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 |
Aug
|
pubmed:issn |
0022-1007
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
182
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pubmed:owner |
NLM
|