Linked Life Data

21372129

Source:http://linkedlifedata.com/resource/pubmed/id/21372129

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2011-4-25
pubmed:abstractText
We previously described a non-classical mechanism that arrests Fc?RIIa signaling in human neutrophils once engaged by immune complexes or opsonized pathogens. The engagement of Fc?RIIa leads to its ubiquitination by the ubiquitin ligase c-Cbl and degradation by the proteasome. Herein, we further examined some of the events regulating this novel pathway. The adaptor protein CIN85 was described in other systems to be involved in the regulation of the c-Cbl-dependent pathway. We found that CIN85 is expressed in human neutrophils and that it translocates like c-Cbl from the cytosol to the plasma membrane following receptor cross-linking. CIN85 was also recruited to the same subset of high density detergent-resistant membrane fractions in which stimulated Fc?RIIa partitioned with c-Cbl. The integrity of these microdomains is essential to the Fc?RIIa degradation process because the cholesterol-depleting agent methyl-?-cyclodextrin inhibits this event. Silencing the expression of CIN85 by siRNA in dibutyryl cyclic AMP-differentiated PLB 985 cells prevented Fc?RIIa degradation and increased IgG-mediated phagocytosis. Confocal microscopy revealed that the presence of CIN85 is essential to the proper sorting of Fc?RIIa during endocytosis. We also provide direct evidence that CIN85 is a substrate of serine/threonine kinase PKCs. Classical PKCs positively regulate Fc?RIIa ubiquitination and degradation because these events were inhibited by Gö6976, a classical PKC inhibitor. We conclude that the ubiquitination and degradation of stimulated Fc?RIIa mediated by c-Cbl are positively regulated by the adaptor protein CIN85 in a PKC-dependent manner and that these events contribute to the termination of Fc?RIIa signaling.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
29
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15073-84
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
CIN85 modulates the down-regulation of Fc gammaRIIa expression and function by c-Cbl in a PKC-dependent manner in human neutrophils.
pubmed:affiliation
Centre de Recherche du CHUQ, Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, Québec G1V 4G2, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't