Signal transduction. FasL binds preassembled Fas

The binding of a ligand to its receptor has always been viewed as the trigger for signal transduction to ensue. However, as Golstein explains in his Perspective, new findings (Chan et al. and Siegel et al.) suggest that the Fas receptor preassembles into trimers without the help of its ligand, and that this preassembly conditions ligand binding, and thus subsequent signal transduction of a death signal.     

Signal transduction. N-WASP regulation--the sting in the tail

Signaling proteins can be regulated by their interactions with other proteins and phospholipids. As Fawcett and Pawson discuss in their Perspective, activation of the N-WASP protein (which coordinates formation of actin filaments) is far more complex, depending on the interaction of N-WASP with both a protein and a phospholipid. The authors explain new results (Prehoda et al.) demonstrating that cooperative binding of the phospholipid PIP2 and the small GTPase Cdc42 to N-WASP results in its activation. The Arp2/3 complex is then able to bind to N-WASP and to proceed with its job of initiating the assembly of actin monomers into actin filaments.     

Signal transduction through prion protein

The cellular prion protein PrPc is a glycosylphosphatidylinositol-anchored cell-surface protein whose biological function is unclear. We used the murine 1C11 neuronal differentiation model to search for PrPc-dependent signal transduction through antibody-mediated cross-linking. A caveolin-1-dependent coupling of PrPc to the tyrosine kinase Fyn was observed. Clathrin might also contribute to this coupling. The ability of the 1C11 cell line to trigger PrPc-dependent Fyn activation was restricted to its fully differentiated serotonergic or noradrenergic progenies. Moreover, the signaling activity of PrPc occurred mainly at neurites. Thus, PrPc may be a signal transduction protein.