Activation of the Ras-related GTPase Rap1 by thymocyte TCR engagement and during selection.
Eur J Immunol
; 30(10): 2832-41, 2000 Oct.
Article
in En
| MEDLINE
| ID: mdl-11069064
ABSTRACT
Signals mediated by activation of the small GTPase Ras play an essential role both in thymocyte development and in TCR-mediated activation of mature T cells. Given the critical requirement of Ras signaling pathways in thymocyte development, and recent indications that Rap1 may negatively regulate Ras-dependent signaling pathways, we examined the possible involvement of Rap1 in thymocyte TCR signaling. We find that Rap1 and proposed regulators of Rap1 (the proto-oncogene product Cbl, Crk family adaptor proteins, and the Rap1 guanine nucleotide exchange factor C3G) are expressed at equivalent levels in both double-negative and double-positive murine thymocytes. Rap1 was transiently activated following TCR stimulation of both total thymocytes and purified double-positive thymocytes, and this activation correlated with tyrosine phosphorylation of Cbl and Cbl association with CrkL. TCR-dependent Rap1 activation was enhanced by co-stimulation through CD28 and could be mimicked by treatment of thymocytes with phorbol ester and calcium. In contrast to mature peripheral T lymphocytes, Rap1 stimulation by CD3 ligation in thymocytes did not require intracellular calcium mobilization. Intriguingly, we found a clear elevation of activated Rap1 in thymocytes undergoing positive selection, suggesting a functional role for Rap1 in thymocyte development and selection.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lymphocyte Activation
/
Receptors, Antigen, T-Cell
/
T-Lymphocytes
/
Rap1 GTP-Binding Proteins
/
Ubiquitin-Protein Ligases
Limits:
Animals
/
Humans
Language:
En
Journal:
Eur J Immunol
Year:
2000
Document type:
Article