Distinct functions of Vav1 in JNK1 activation in Jurkat T cells versus non-haematopoietic cells

Kaminski, S.; Del Pozo, M. A.; Hipskind, R. A.; Altman, A.; Villalba, M.

Scand J Immunol

2004-06 / vol 59 / pages 527-35


Vav1, the 95-kDa protein encoded by the vav1 proto-oncogene, is expressed exclusively in haematopoietic cells, where it becomes phosphorylated on tyrosine residues in response to antigen receptor ligation. Vav1 was found to act as a Rac1-specific guanine nucleotide exchange factor and to activate c-Jun N-terminal kinase (JNK1) in vitro and in ectopic expression systems using non-haematopoietic cells. Here, we studied the role of Vav1 in JNK1 activation in T cells versus non-haematopoietic cells. Vav1 overexpression activated JNK1 in COS7 and 293T cells but not in Jurkat T lymphocytes. In contrast, constitutively activated Rac1 efficiently stimulated JNK1 in both cell types under the same conditions. Vav1 did function in T cells because it clearly stimulated the activity of a nuclear factor of activated T-cell reporter plasmid in the same cells. Moreover, Vav1 induction of JNK1 in T cells required coexpression with calcineurin. This cooperation was cell type specific because it was not observed in COS7 or 293T cells. In contrast, Vav1 did not cooperate with calcineurin to activate either extracellular signal-regulated kinase 2 or p38. These findings demonstrate that Vav1 alone is a poor activator of the JNK1 pathway in T cells and emphasize the importance of studying the physiological functions of Vav1 in haematopoietic cells.

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Humans; Animals; Calcineurin/metabolism; Transfection; Lymphocyte Activation/immunology; Mitogen-Activated Protein Kinases/*metabolism; Cercopithecus aethiops; COS Cells; Jurkat Cells; T-Lymphocytes/*immunology; p38 Mitogen-Activated Protein Kinases; Signal Transduction/*immunology; Mitogen-Activated Protein Kinase 8; Oncogene Proteins/*metabolism; Proto-Oncogene Proteins c-vav; rac1 GTP-Binding Protein/metabolism

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