Source:http://linkedlifedata.com/resource/pubmed/id/20357244
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
23
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| pubmed:dateCreated |
2010-6-11
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| pubmed:abstractText |
In the disorder leukocyte adhesion deficiency III (LAD-III), integrins on platelets and leukocytes are expressed but fail to function and this leads to severe bleeding and infections at an early age. Mutation in the KINDLIN3 (FERMT3) gene is the cause of LAD-III in patients from the Middle East, Malta, and Turkey. We describe 2 novel homozygous mutations in the KINDLIN3 gene of a new African-American patient that destabilize KINDLIN3 mRNA leading to loss of kindlin-3 protein. Transfection of wild-type (WT) KINDLIN3 cDNA restored integrin-related adhesion and migration in the LAD-III patient's T and B lymphocytes. We analyzed the individual mutations separately in vitro to learn more about the function of the kindlin-3 protein. The first G>A mutation gives rise to a Gly308Arg change at the end of FERM (protein 4.1, ezrin, radixin, moesin) subdomain 2, and the second mutation is a base deletion causing early termination within the pleckstrin homology (PH) domain. This second mutation prevented membrane association of kindlin-3 and did not restore either adhesion or migration, whereas the FERM subdomain 2 mutation affected only migration. Thus, these LAD-III patient mutations have highlighted functionally important regions of kindlin-3 that alter leukocyte integrin-dependent function in 2 distinct ways.
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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/Integrins,
http://linkedlifedata.com/resource/pubmed/chemical/MIG2B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
1528-0020
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
10
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| pubmed:volume |
115
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
4834-42
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| pubmed:meshHeading |
pubmed-meshheading:20357244-African Americans,
pubmed-meshheading:20357244-Amino Acid Substitution,
pubmed-meshheading:20357244-B-Lymphocytes,
pubmed-meshheading:20357244-Cell Adhesion,
pubmed-meshheading:20357244-Cell Movement,
pubmed-meshheading:20357244-Female,
pubmed-meshheading:20357244-Genetic Diseases, Inborn,
pubmed-meshheading:20357244-Homozygote,
pubmed-meshheading:20357244-Humans,
pubmed-meshheading:20357244-Infant,
pubmed-meshheading:20357244-Integrins,
pubmed-meshheading:20357244-Leukocyte-Adhesion Deficiency Syndrome,
pubmed-meshheading:20357244-Membrane Proteins,
pubmed-meshheading:20357244-Mutation, Missense,
pubmed-meshheading:20357244-Neoplasm Proteins,
pubmed-meshheading:20357244-Protein Structure, Tertiary,
pubmed-meshheading:20357244-RNA, Messenger,
pubmed-meshheading:20357244-RNA Stability,
pubmed-meshheading:20357244-T-Lymphocytes
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| pubmed:year |
2010
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| pubmed:articleTitle |
Two mutations in the KINDLIN3 gene of a new leukocyte adhesion deficiency III patient reveal distinct effects on leukocyte function in vitro.
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| pubmed:affiliation |
Leukocyte Adhesion Laboratory, Cancer Research UK London Research Institute, London, UK.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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