Table 2.

Key regulators of vascular lumen formation in 3D matrices (II)

Regulator	Functional properties	Interacting partners	References
VE-cadherin	Regulator of cell-cell junctions and other signaling functions; controls formation of lumens and/or facilitates lumen maintenance; plays a role in directing vacuoles to the EC apical membrane surface	Binds (3-catenin and CSK, a negative regulator of EC lumen formation; interacts with Par3 to facilitate EC polarization and lumen formation/maintenance	Carmeliet et al, 1999; Yang etal, 1999; Koh et al, 2009; Strilic et al, 2009; Wang etal, 2010; Lampugnani et al, 2010
CCM1, CCM2, CCM3	These three proteins form a complex of proteins which is altered in the human disease CCM; CCM1, CCM2, and CCM3 control EC lumen formation	CCM1, CCM2, and CCM3 interact; CCM1 is a RapGEF and CCM2 can bind (3-catenin; CCM3 binds STK kinases; siRNA suppression of CCM1 or CCM2 leads to marked RhoA activation	Whitehead et al, 2009; Kleaveland et al, 2009; Stockton etal, 2010; Lampugnani et al, 2010; Chan etal, 2011
Rasipl	An EC-specific gene that when deleted from mice or suppressed in human ECs leads to marked blockade of lumen formation; siRNA suppression of Rasip leads to strongly reduced Cdc42 and Racl activation and increased RhoA activation in 3D matrices (leads to inhibition of lumen formation)	Binds to Arhgap29, a Rho-specific GAP, Myh9 (myosin II) and Ras; Rasipl appears to coordinate small GTPase signaling and affects EC cytoskeletal and adhesive functions to control vascular morphogenesis	Xu et al, 2009, 2011
Moesin	Can control EC lumen formation through EC vacuole formation and targeting of vacuoles to the apical surface; activated downstream of CCM proteins; possible negative regulator of RhoA activation	Moesin can target to actin-rich plasma membranes such as those on the apical surface or intracellular vacuole membranes; activated by STK kinases (e.g. STK25) which control lumen formation	Strilic et al, 2009; Wang etal, 2010; Zheng etal, 2010; Chan etal, 2011
PKCe.aPKC, Src, Yes, Pak-2, Pak-4, C-Raf, B-Raf, Mekl, Erkl/2, STKs	Kinase cascades control EC lumen and tube formation; integrin- and Cdc42/Racl-dependent signaling stimulate these kinases to regulate the lumen formation process in 3D matrices	PKCe activates Src and then activates Pak-2 and Pak-4, etc., to stimulate the lumen formation cascade; blockade of either PKCe or Src disrupts EC lumen formation and dissociates the EC lumen signaling complex	Koh et al, 2008a, 2009; Zheng etal, 2010; Sacharidou et al, 2010; Chan etal, 2011