No evidence for involvement of mouse protein-tyrosine phosphatase-BAS-like Fas-associated phosphatase-1 in Fas-mediated apoptosis.
Recently, one of the PDZ domains in the cytosolic protein-tyrosine phosphatase Fas-associated phosphatase-1 (FAP-1)/protein-tyrosine phosphatase-BAS (PTP-BAS) was shown to interact with the carboxyl-terminal tS-L-V peptide of the human Fas receptor (Sato, T., Irie, S., Kitada, S., and Reed, J. C. (1995) Science 268, 411-415), suggesting a role for protein (de)phosphorylation in Fas signaling. To investigate whether this interaction is conserved in mouse, we performed yeast two-hybrid interaction experiments and transfection studies in mouse T cell lines. For the corresponding PDZ motif in the mouse homologue of FAP-1/PTP-BAS, protein-tyrosine phosphatase-BAS-like (PTP-BL), only an interaction with human but not with mouse Fas could be detected. Presence of the tS-L-V motif proper, which is unique for human Fas, rather than the structural context of its carboxyl terminus, apparently explains the initially observed binding. To test for functional conservation of any indirect involvement of PTP-BL in Fas-mediated signaling, we generated T lymphoma cell lines stably expressing mouse or human Fas receptor with and without PTP-BL. No inhibitory effect of PTP-BL was observed upon triggering apoptosis using mouse or human Fas-activating antibodies. Together with the markedly different tissue expression patterns for PTP-BL and Fas receptor, our findings suggest that protein-tyrosine phosphatase PTP-BL does not play a key role in the Fas-mediated death pathway.
Cuppen
E
E
Department of Cell Biology and Histology, Institute of Cellular Signaling, University of Nijmegen, P. O. Box 9101, 6500 HB Nijmegen, The Netherlands. w.hendriks@celbi.kun.nl
Nagata
S
S
Wieringa
B
B
Hendriks
W
W
D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D053222:Fas Ligand Protein; D015870:Gene Expression; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D011485:Protein Binding; D054645:Protein Phosphatase 1; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014018:Tissue Distribution; D019014:fas Receptor / Q000502:physiology*
D002352:Carrier Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor; D054645:Protein Phosphatase 1; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases; C516743:Ptpn13 protein, mouse