Vav1 oncogenic mutation inhibits T cell receptor-induced calcium mobilization through inhibition of phospholipase Cγ1 activation.
J Biol Chem
; 287(23): 19725-35, 2012 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-22474331
ABSTRACT
Robust elevation of the cytosolic calcium concentration is a crucial early step for T cell activation triggered by the T cell antigen receptor. Vav1 is a proto-oncogene expressed in hematopoietic cells that is indispensable for transducing the calcium-mobilizing signal. Following T cell receptor stimulation, Vav1 facilitates formation of signaling microclusters through multiple interactions with other proteins participating in the signaling cascade. Truncation of the N terminus of Vav1 produces its oncogenic version, which is unable to support normal calcium flux following T cell activation. We show here that truncation of the N-terminal region of Vav1 alters the fine structure of protein complexes in the signaling clusters, affecting the interaction of Vav1 with phospholipase Cγ1 (PLCγ1). This alteration is accompanied by a decrease in PLCγ1 phosphorylation and inhibition of inositol 1,4,5-trisphosphate production. We suggest that the structural integrity of the N-terminal region of Vav1 is important for the proper formation of the Vav1-associated signaling complexes. The oncogenic truncation of this region elicits conformational changes that interfere with the Vav1-mediated activation of PLCγ1 and that inhibit calcium mobilization.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Receptores de Antígenos de Linfocitos T
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Linfocitos T
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Calcio
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Fosfolipasa C gamma
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Proteínas Proto-Oncogénicas c-vav
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Mutación
Límite:
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2012
Tipo del documento:
Article
País de afiliación:
Israel