Leukemia apoptosis sensitivity decreased by Fas phosphorylation

09-11-2006

A decrease in sensitivity to apoptosis in the Jurkat T leukemia cell line could be due in part to Fas phosphorylation.

According to a study from France, "Apoptosis signalling through the Fas pathway requires several steps of aggregation of the Fas receptor in the membrane, including aggregation that may occur in the absence of Fas ligand. Association of Fas domains is determinant to signal transmission following Fas ligand binding to a specific domain."

"The domains involved in Fas aggregation are located in its extracellular region and contain 3 potential protein kinase C-binding motifs," explained C. Lautrette and colleagues, University Hospital. "We therefore studied the possibility that phosphorylation of the extracellular region of Fas might be implicated in the regulation of Fas-mediated apoptosis. Inhibition experiments of extracellular phosphorylation were performed in human Jurkat T leukemia cells with K252b, an impermeant protein-kinase inhibitor.

"Extracellular phosphorylation of Fas receptor was related to ecto-kinase, as assessed by the [gamma-P-32] ATP labelling of Fas-116 kDa aggregates, suppressed by K252b inhibitor which significantly increased the sensitivity to Fas-mediated apoptosis. Ecto-PKC involvement was demonstrated by bisindolylmaleimide VIII, a selective inhibitor of protein kinase C which significantly increased both Fas aggregation in the membrane and Fas-mediated apoptosis and by the addition of the PKC pseudo-substrate 19-36 which inhibited the phosphorylation of 116 kDa Fas aggregates."

The researchers concluded, "These data support a role for Fas phosphorylation in the decreased sensitivity to apoptosis in the Jurkat T leukemia cell line."

Lautrette and colleagues published the results of their research in Apoptosis (Increase of Fas-induced apoptosis by inhibition of extracellular phosphorylation of Fas receptor in Jurkat cell line. Apoptosis, 2006;11(7):1195-1204).

For additional information, contact M.O. Jauberteau, University Hospital, Immunology Laboratory, 2 Avenue Martin Luther King, F-87042 Limoges, France.

The publisher of the journal Apoptosis can be contacted at: Springer, Van Godewijckstraat 30, 3311 Gz Dordrecht, Netherlands.

Keywords: Limoges, France, Apoptosis, Ectoprotein Kinase, Fas Phosphorylation, Leukemia, Protein Kinase C, Proteins, Proteomics, T Leukemia Cell Jurkat.

This article was prepared by Hematology Week editors from staff and other reports. Copyright 2006, Hematology Week via NewsRx.com.