Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening.

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Voss M, Lettau M, Janssen O

Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening.

BMC Immunol. 2009 Oct 6;10:53. doi: 10.1186/1471-2172-10-53.

PubMed ID
19807924 [ View in PubMed
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Abstract

BACKGROUND: Fas ligand is a cytotoxic effector molecule of T and NK cells which is characterized by an intracellular N-terminal polyproline region that serves as a docking site for SH3 and WW domain proteins. Several previously described Fas ligand-interacting SH3 domain proteins turned out to be crucial for the regulation of storage, expression and function of the death factor. Recent observations, however, indicate that Fas ligand is also subject to posttranslational modifications including shedding and intramembrane proteolysis. This results in the generation of short intracellular fragments that might either be degraded or translocate to the nucleus to influence transcription. So far, protein-protein interactions that specifically regulate the fate of the intracellular fragments have not been identified. RESULTS: In order to further define the SH3 domain interactome of the intracellular region of Fas ligand, we now screened a human SH3 domain phage display library. In addition to known SH3 domains mediating binding to the Fas ligand proline-rich domain, we were able to identify a number of additional SH3 domains that might also associate with FasL. Potential functional implications of the new binding proteins for the death factor's biology are discussed. For Tec kinases and sorting nexins, the observed interactions were verified in cellular systems by pulldown experiments. CONCLUSION: We provide an extended list of putative Fas ligand interaction partners, confirming previously identified interactions, but also introducing several novel SH3 domain proteins that might be important regulators of Fas ligand function.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Proto-oncogene tyrosine-protein kinase SrcP12931Details
Tyrosine-protein kinase FynP06241Details
Tyrosine-protein kinase YesP07947Details
Phosphatidylinositol 3-kinase regulatory subunit alphaP27986Details
Tyrosine-protein kinase BTKQ06187Details
Tyrosine-protein kinase ITK/TSKQ08881Details
Tyrosine-protein kinase HCKP08631Details
Voltage-dependent L-type calcium channel subunit beta-4O00305Details
Voltage-dependent L-type calcium channel subunit beta-3P54284Details
Tyrosine-protein kinase LynP07948Details
Neutrophil cytosol factor 1P14598Details
Tyrosine-protein kinase TecP42680Details