Regulating Vav1 phosphorylation by the SHP-1 tyrosine phosphatase is a fine-tuning mechanism for the negative regulation of DISC formation and Fas-mediated cell death signaling.
The actin cytoskeleton association is required for caspase 8-independent Fas/CD95 receptor internalization, a critical step for an optimal death-inducing signaling complex formation along the endocytic pathway, leading to efficient activation of the caspase cascade and, ultimately, cell death. However, the way in which this initiation phase of Fas receptor signaling is regulated is still unknown. We report herein that, in B cells, upon Fas engagement, the tyrosine phosphatase SHP-1-regulated Vav dephosphorylation, by downmodulating the Fas-ezrin-actin linkage is a fine-tune switch-off mechanism that the cell uses as a way to terminate the receptor internalization, controlling therefore the time and extent of the DISC formation and cell death.
Koncz
G
G
Equipe Labelisée La Ligue, Institute of Signalling, Developmental Biology and Cancer Research, CNRS UMR 6543, Nice, France.
Kerekes
K
K
Chakrabandhu
K
K
Hueber
A-O
AO
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism*; D015398:Signal Transduction; D019014:fas Receptor / Q000378:metabolism*; D000099149:Ezrin
D003598:Cytoskeletal Proteins; D053418:Death Domain Receptor Signaling Adaptor Proteins; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D051567:Proto-Oncogene Proteins c-vav; D019014:fas Receptor; D000099149:Ezrin; C496619:Vav1 protein, mouse; C509248:Ptpn6 protein, mouse