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 S
The application of high-throughput genomic approaches has revealed 24 novel risk loci for Alzheimer’s disease (AD). We recently reported that the bridging integrator 1 (BIN1) risk gene is linked to Tau pathology.
Phage display procedure was applied to the N-terminal domain of human topoisomerase I. The consensus sequence identified for clones binding to the N-terminal domain was found in 35 human proteins that are either permanently or temporarily located in
The SH3 domain family is one of the most representative and widely studied cases of so-called Peptide Recognition Modules (PRM). The polyproline II motif PxxP that generally characterizes its ligands does not reflect the complex interaction spectrum
X-linked agammaglobulinemia (XLA), an inherited disease, is caused by mutations in the Bruton's tyrosine kinase (BTK). The absence of functional BTK leads to failure of B cell differentiation which incapacitates antibody production in XLA patients le
Ras–GTPase activating protein SH3 domain-binding proteins 1 and 2 (G3BP1 and G3BP2) have recently been reported to be encoded by two separate genes on human chromosomes 5 and 4 respectively and have been implicated in Ras signalling, NFkappaB signall
The solution structure of the SH3 domain of human p56 Lck tyrosine kinase (Lck-SH3) has been determined by multidimensional heteronuclear NMR spectroscopy. The structure was calculated from a total of 935 experimental restraints comprising 785 distan
Src Homology 2 and 3 (SH2 and SH3) are two key protein interaction modules involved in regulating the activity of many proteins such as tyrosine kinases and phosphatases by respective recognition of phosphotyrosine and proline-rich regions. In the Sr
Cell Communication and Signaling
Identification of SH3 domain interaction partners of FasL using a human SH3 domain phage display library M Voss*, O Janssen and M Lettau Address: Medical Center Schleswig-Holstein Campus Kiel, Institute for Immunology, Molecular Immunology, Kiel, Gemany * Corresponding author
from 12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes Weimar, Germany. 29–31 October 2008 Published: 26 February 2009 Cell Communication and Signaling 2009, 7(Suppl 1):A92
12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes
Frank Entschladen, Karlheinz Friedrich, Ralf Hass and Ottmar JanssenMeeting abstracts – A single PDF containing all abstracts in this Supplement is available here.
Unlike other members of the tumour necrosis factor superfamily, Fas ligand (CD95L) contains a unique polyproline region (aa 37–70) as part of its N-terminal intracellular tail. We already described several SH3 or WW domain proteins that proved to interact with FasL via this proline-rich domain (PRD). We defined distinct adapter proteins that are involved in the regulation of FasL sorting and trafficking and identified ADAM10 as the FasL sheddase (see  for review). Given that ADAM10-mediated ectodomain shedding regulates the surface expression of FasL and that FasL is subsequently released into the cytosol by regulated intramembrane proteolysis (RIPing) through the γ-secretase-like enzyme SPPL2a, we are interested in defining interactions involving the generated intracellular fragment of FasL. Interestingly, so far we failed to co-immunoprecipitate either the FasL N-terminal membrane fragments generated by ADAM10 cleavage or the FasL intracellular remainder generated by SPPL2a activity with previously described interaction partners, while full length FasL was co-immunoprecipitated. From precipitates with a new mAb directed against the intracellular portion of FasL, however, we can readily detect processed FasL in T cell blasts. In order to identify other SH3 domain proteins that potentially (and selectively?) interact with the RIPed FasL PRD, we used a SH3 domain phage display library containing all 288 SH3 domains expressed in humans. We are thus confident to be able to present the complete "SH3 interactome" for the FasL PRD in Weimar. The identification of interactors will give us some hints on the still open function of the intracellular FasL fragments.
Acknowledgements Sponsored by the DFG (SFB415, to OJ) and the Medical Faculty of the Christian-Albrechts University of Kiel (to ML).
Lettau M, et al.: Storage, expression and function of Fas ligand, the key death factor of immune cells. Curr Med Chem 2008, 15:1684-1696.
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