Linked Life Data

21757698

Source:http://linkedlifedata.com/resource/pubmed/id/21757698

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
35
pubmed:dateCreated
2011-8-29
pubmed:abstractText
We examined over 50 mutations in the Drosophila ?PS integrin subunit that alter integrin function in situ for their ability to bind a soluble monovalent ligand, TWOW-1. Surprisingly, very few of the mutations, which were selected for conditional lethality in the fly, reduce the ligand binding ability of the integrin. The most prevalent class of mutations activates the integrin heterodimer. These findings emphasize the importance of integrin affinity regulation and point out how molecular interactions throughout the integrin molecule are important in keeping the integrin in a low affinity state. Mutations strongly support the controversial deadbolt hypothesis, where the CD loop in the ? tail domain acts to restrain the I domain in the inactive, bent conformation. Site-directed mutations in the cytoplasmic domains of ?PS and ?PS2C reveal different effects on ligand binding from those observed for ?IIb?3 integrins and identify for the first time a cytoplasmic cysteine residue, conserved in three human integrins, as being important in affinity regulation. In the fly, we find that genetic interactions of the ?PS mutations with reduction in talin function are consistent with the integrin affinity differences measured in cells. Additionally, these genetic interactions report on increased and decreased integrin functions that do not result in affinity changes in the PS2C integrin measured in cultured cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
2
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
30981-93
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Identification of integrin beta subunit mutations that alter affinity for extracellular matrix ligand.
pubmed:affiliation
Department of Molecular and Cellular Biology, Arizona Cancer Center, Tucson, Arizona 85724, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural