Table 1. Abl family kinase targets involved in vascular barrier function.
Multiple targets of c-Abl and Arg have established roles in the regulation of vascular permeability, which are briefly described. A complete listing of known Abl kinase substrates is available in a recent comprehensive review14.
| Protein | Function in Vascular Barrier Function |
|---|---|
| c-Abl | Mediates vascular leak downstream of edemagenic agents via effects on AJs and nmMLCK activation11 Attenuates vascular leak downstream of S1P and FTY720 via effects on cortactin and nmMLCK phosphorylation40 |
| Arg | Mediates vascular leak downstream of edemagenic agents via effects on FAs and Rac activity78 |
| β-Catenin | Binds to VE-Cadherin, which structurally and functionally couples AJs to the actin cytoskeleton15 |
| Cav1 | Major component of caveolae, which are responsible for transcellular transport of fluid and albumin80 |
| Crk & CrkL | Adaptor proteins involved in AJ remodeling48 Crk phosphorylation is involved in Rac activation and unphosphorylated Crk promotes AJ disassembly49 |
| Cortactin | Attenuates vascular leak by promoting actin polymerization at lamellipodia81 |
| nmMLCK | Central mediator of permeability via effects on actin-myosin contraction and ultimately cell shape. Involved in formation of both stress fibers and lamellipodia depending on subcellular localization3 |
| Myosin IIB | Component of actin-myosin contractile apparatus3 |
| p190RhoGAP | Associates with p120RhoGEF as part of a complex that inhibits Rho activity, decreases actomyosin contractility, and focal adhesion remodeling6–8, 29 |
| Paxillin | Component of FAs that binds to the integrin cytoplasmic tail, serving as a link to the actin cytoskeleton15 |
| WAVE2/3 & N-WASP | Promote actin polymerization at lamellipodia3 |