Association of the EF-hand and PH domains of the guanine nucleotide exchange factor SLAT with IP3 receptor 1 promotes Ca²âº signaling in T cells.
Sci Signal
; 7(345): ra93, 2014 Sep 30.
Article
en En
| MEDLINE
| ID: mdl-25270259
ABSTRACT
The guanine nucleotide exchange factor SLAT (SWAP-70-like adaptor of T cells) regulates T cell activation and differentiation by enabling Ca(2+) release from intracellular stores in response to stimulation of the T cell receptor (TCR). We found a TCR-induced association between SLAT and inositol 1,4,5-trisphosphate (IP3) receptor type 1 (IP3R1). The N-terminal region of SLAT, which contains two EF-hand motifs that we determined bound Ca(2+), and the SLAT pleckstrin homology (PH) domain independently bound to IP3R1 by associating with a conserved motif within the IP3R1 ligand-binding domain. Disruption of the SLAT-IP3R1 interaction with cell-permeable, IP3R1-based fusion peptides inhibited TCR-stimulated Ca(2+) signaling, activation of the transcription factor NFAT (nuclear factor of activated T cells), and production of cytokines, suggesting that this interaction is required for optimal T cell activation. The finding that SLAT is an IP3R1-interacting protein required for T cell activation suggests that this interaction could be a potential target for a selective immunosuppressive drug.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Nucleares
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Activación de Linfocitos
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Linfocitos T
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Señalización del Calcio
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Proteínas de Unión al ADN
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Receptores de Inositol 1,4,5-Trifosfato
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Año:
2014
Tipo del documento:
Article