Modular protein-protein interaction domains convey signals from activated receptors using a variety of recognition motifs. Both the TNF and FGF receptors employ modular protein-protein interaction domains to convey signals. The activated TNF-R1 trimer binds a docking protein, TRADD, through death domain (DD)-DD interactions. TRAD, in turn, binds to a variety of adaptors, including FADD, TRAFs and RIP. FADD recruits pro-caspase 8 which initiates a proteolytic cascade resulting in apoptosis. Recruitment of TRAF-2 via the TRAF-C domain initiates the Jnk pathway, while recruitment of RIP activates NFkB signaling. In an analogous manner, the FGF-R is clustered by FGF and proteoglycan. The myristoylated FRS2 scaffold protein binds to the FGF-R through its PTB domain, becomes phosphorylated on multiple tyrosines, and consequently binds the SH2 proteins Grb2 and Shp2. The Grb2 adaptor recruits Sos1 through its SH3 domain, and Sos1 acts as a GEF for the Ras GTPase. Activated Ras can potentially stimulate multiple pathways to promote cell survival, activate transcription or cause cytoskeletal rearrangement.
Copyright © 2001-2014 Daniele Focosi.
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