Fig. 8. Dissection of the signaling pathway activated by preconditioning and leading to lysosome-plasma membrane fusion. The scheme proposed is based on our previous (Carini et al., 2001a) and present data. Stimulation of the adenosine A₂ receptor activates a cascade of signals involving PI3K, PKC and p38MAPK that eventually impact on the vesicular traffic. Consequently, endosomal and lysosomal organelles are translocated to the periphery of the cell and fuse with the plasma membrane in a calcium-dependent fashion. This process requires the integrity of the cytoskeleton and results in the exocytic insertion of lysosomal mebrane proteins on the plasma membrane. ER, endoplasmic reticulum; GC, Golgi complex; PLC, phospholipase C; DAG, diacylglycerol; IP3, inositol (1,4,5) tris-phosphate.