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Title

p85β phosphoinositide 3-kinase regulates CD28 coreceptor function

AuthorsAlcázar, Isabela; Cortés, Isabel; Zaballos, Ángel; Hernández, Carmen; Fruman, David A.; Barber, Domingo F.; Carrera, Ana C.
Issue Date3-Feb-2009
PublisherAmerican Society of Hematology
CitationBlood 113(14): 3198-3208 (2009)
AbstractCD28 is a receptor expressed on T cells that regulates their differentiation after antigen stimulation to long-term-survival memory T cells. CD28 enhances T-cell receptor signals and reduces expression of CBL ubiquitin ligases, which negatively control T-cell activation. In the absence of CD28 ligation during the primary stimulation, CBL levels remain high and T cells fail to mount an efficient secondary response. CD28 associates with p85, one of the regulatory subunits of phosphoinositide-3-kinase (PI3K), but the relevance of this interaction is debated. We examined here the contribution of the other ubiquitous PI3K regulatory subunit, p85β, in CD28 function. We describe that p85β bound to CD28 and to CBL with greater affinity than p85. Moreover, deletion of p85β impaired CD28-induced intracellular events, including c-CBL and CBL-b down-regulation as well as PI3K pathway activation. This resulted in defective differentiation of activated T cells, which failed to exhibit an efficient secondary immune response. Considering that p85β-deficient T cells fail in recall responses and that p85β binds to and regulates CD28 signals, the presented observations suggest the involvement of p85β in CD28-mediated activation and differentiation of antigen-stimulated T cells.
Description11 pages.-- PMID: 19190244 [PubMed].-- Printed version published Apr 2, 2009.
Supporting information available at: http://bloodjournal.hematologylibrary.org/cgi/content/full/blood-2008-04-152942/DC1
Publisher version (URL)http://dx.doi.org/10.1182/blood-2008-04-152942
URIhttp://hdl.handle.net/10261/13179
DOI10.1182/blood-2008-04-152942
ISSN0006-4971
Appears in Collections:(CNB) Artículos
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