Prohibitins function as endogenous ligands for Siglec-9 and negatively regulate TCR signaling upon ligation.
Biochem Biophys Res Commun
; 434(2): 376-81, 2013 May 03.
Article
em En
| MEDLINE
| ID: mdl-23567969
ABSTRACT
Previously we demonstrated that prohibitin-1 and -2 (prohibitins) were expressed on the surface of T cell leukemia cell lines and activated T lymphocytes. In the present study, we found that prohibitins play a role as counter receptors for Siglec-9 expressed on macrophages and dendritic cells. Siglec-9 bound to prohibitins in a sialic acid-independent manner. Mutated Siglec-9 with Arg(120) changed to Ala lost the binding activity, suggesting a specific ionic peptide-peptide interaction. Phosphorylation of ERK1/2 in Jurkat cells on treatment with anti-CD3 antibody immobilized beads was markedly diminished on treatment with anti-CD3 antibody and Siglec-9 co-immobilized beads, indicating that engagement of prohibitins with Siglec-9 inhibits ERK1/2 phosphorylation. Phosphorylation of c-Raf was also reduced, maybe due to inhibition of the c-Raf-prohibitin interaction by Siglec-9 ligation. In parallel with inhibition of the ERK cascade, IL-2 production was markedly decreased in Jurkat cells. Thus, this interaction may be a useful immunotherapeutic target.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Receptores de Antígenos de Linfócitos T
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Sistema de Sinalização das MAP Quinases
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Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article