Fig. 4. Differential regulation of the vascular barrier by PECAM-1 isoforms.

(a) Δ15 PECAM-1 retains the ITIM tyrosines, which enables it to recruit SHP-2 and inhibit Src (dashed line). Src no longer activates MAPK/ERKs which stabilizes expression of PECAM-1 and VE-cadherin at the endothelial cell junction. (b) In contrast, Δ14, 15 PECAM-1 does not contain the ITIM, thus the inhibition on Src is relieved, which activates MAPK/ERKs (solid line) leading to decreased expression of PECAM-1 and VE-cadherin and turnover of focal adhesion complexes. This destabilizes the junction and creates a more migratory phenotype.