Volume 272, Number 48, Issue of November 28, 1997 pp. 30215-30220
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

No Evidence for Involvement of Mouse Protein-tyrosine Phosphatase-BAS-like Fas-associated Phosphatase-1 in Fas-mediated Apoptosis

(Received for publication, July 15, 1997)

Edwin Cuppen , Shigekazu Nagata ^§ , Bé Wieringa and Wiljan Hendriks

From the  Department of Cell Biology and Histology, Institute of Cellular Signaling, University of Nijmegen, P. O. Box 9101, 6500 HB Nijmegen, The Netherlands and the ^§ Department of Genetics, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565, Japan

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.

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