Spatial organization of EGF receptor transmodulation by PDGF

Even though the modulation of EGF receptors by PDGF is well documented, it is not known where on the cell surface cross-talk between the two receptor systems takes place. The recent finding that both populations of receptors are concentrated in cell surface caveolae suggests that the confinement of the two receptors to this space might facilitate their interaction. Here we show that stimulation of PDGF receptors in caveolae with PDGF causes a sub population of EGF receptors in the same membrane fraction to become phospho rylated on tyrosine, Coincident with tyrosine phosphorylation, the binding of EGF to its receptor markedly declines. Loss of EGF binding is partially blocked by tyrosine kinase inhibitors. Despite the close proximity of the t wo receptors in caveolae, we saw no evidence that EGF could stimulated PDGF R tyrosine phosphorylation. These results suggest that these two receptor s ystems are highly organized in caveolae. (C) 1999 Academic Press.