Schematic representation of some signaling networks that control the formation of actin stress fibers at adherens junctions in endothelial cells. VE-cadherin can directly or indirectly recruit regulators of actin polymerization, among which is the small GTPase Rac as well as regulators of Rac and Rho. Regulators include Rac activators, such as the small GPTPase Rap1 (linked through CCM1 and β-catenin) and its guanine-exchange factor, PDZ-GEF (linked through MAGI and β-catenin), the Rac guanine-exchange factor Tiam (through the local activation of phosphoinositide 3-kinase (PI3K), and Vav2. Tiam and Rac can be localized at junctions also through the Par polarity complex (not shown in the figure) . Rho inhibitors include CCM2 (linked through CCM1 and β-catenin and down-regulating Rho activity through a still poorly defined mechanism) and p190RhoGAP (linked through p120). Rap1 can convey signals from cAMP, through its GEF, Epac . Therefore, local clustering of VE-cadherin as well as regulation of the association of β-catenin and p120 to VE-cadherin appears crucial to the assembly of a molecular unit controlling actin polymerization and contraction at junctions. Pharmacological tools to modulate this complex might be of therapeutic relevance.
Lampugnani Journal of Biology 2010 9:16 doi:10.1186/jbiol232