TY  - JOUR
A1  - Baum, Wiebke
A1  - Kirkin, Vladimir
A1  - Mateus Fernández, Sara
A1  - Pick, Robert
A1  - Lettau, Marcus
A1  - Janssen, Ottmar Johannes
A1  - Zörnig, Martin
T1  - Binding of the intracellular Fas ligand (FasL) domain to the adaptor protein PSTPIP results in a cytoplasmic localization of FasL
T2  - Journal of biological chemistry
N2  - The tumor necrosis factor family member Fas ligand (FasL) induces apoptosis in Fas receptor-expressing target cells and is an important cytotoxic effector molecule used by CTL- and NK-cells. In these hematopoietic cells, newly synthesized FasL is stored in specialized secretory lysosomes and only delivered to the cell surface upon activation and target cell recognition. FasL contains an 80-amino acid-long cytoplasmic tail, which includes a proline-rich domain as a bona fide Src homology 3 domain-binding site. This proline-rich domain has been implicated in FasL sorting to secretory lysosomes, and it may also be important for reverse signaling via FasL, which has been described to influence T-cell activation. Here we report the identification of the Src homology 3 domain-containing adaptor protein PSTPIP as a FasL-interacting partner, which binds to the proline-rich domain. PSTPIP co-expression leads to an increased intracellular localization of Fas ligand, thereby regulating extracellular availability and cytotoxic activity of the molecule. In addition, we demonstrate recruitment of the tyrosine phosphatase PTP-PEST by PSTPIP into FasL·PSTPIP·PTP-PEST complexes which may contribute to FasL reverse signaling.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76204
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-762042
SN  - 0021-9258
VL  - 280.2005
IS  - 48
SP  - 40012
EP  - 40024
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -