Figure 6.

Schematic summary of findings. Ephrin-B2 sequesters PDGFRβ into caveolin-1-positive membrane domains and thereby counteracts clathrin-mediated endocytosis and excessive activation of the RTK. In particular, this process limits PDGF-B-induced Erk1/2 and JNK activation. Accordingly, down-regulation of ephrin-B2 levels (for example, via EphB-induced internalization through interactions with other VSMCs) enhances Erk1/2 and JNK signaling in response to PDGF-B. At the same time, ephrin-B2 positively regulates Tiam1 expression and thereby PDGF-B-induced Rac1 activation. MAP kinase overactivation reduces Tiam1 transcript levels and protein, which leads to impaired smooth muscle cell spreading and proliferation.