Phosphorylation of KDR (VEGFR2) and FLT4 (VEGFR3) and PECAM1 in PECAM1:CDH5:KDR:FLT4:CTNNB1

Stable Identifier
R-HSA-9860500
Type
Reaction [uncertain]
Species
Homo sapiens
Compartment
cytosol, plasma membrane
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Phosphorylation of KDR (VEGFR2) and FLT4 (VEGFR3) and PECAM1 in PECAM1:CDH5:KDR:FLT4:CTNNB1
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
Both KDR (VEGFR2) and FLT4 (VEGFR3) bind CDH5 (VE-cadherin) and are located in a mechanosensory complex with CDH5, PECAM1, and CTNNB1 (beta-catenin) on the plasma membrane between adjacent endothelial cells (Coon et al. 2015). KDR (Tzima t al. 2005), FLT4, (Coon et al. 2015) and PECAM1 (Chiu et al. 2008, and inferred from the bovine homolog) are rapidly phosphorylated in response to laminar shear flow across endothelial cells. The order of phosphorylations and the responsible kinases are uncertain, though SRC family kinases seem to be required and both FYN (Chiu et al. 2008) and SRC (inferred from bovine homologs) have been demonstrated to phosphorylate PECAM1.
The phosphorylation of KDR in response to shear flow is also observed for bovine KDR (FLK-1) in bovine endothelial cells (Chen et al. 1999 , Shay-Salit et al. 2002, and Jin et al. 2003). Shear flow causes KDR to cluster on the lumenal plasma membrane of bovine aortic endothelial cells (Chen et al. 1999) and associate with CDH5 (VE-cadherin) and CTNNB1 (beta-catenin) (Shay-Salit et al. 2002). The clustering may be the cause of the ligand-independent activation of KDR in response to shear flow.
Literature References
PubMed ID Title Journal Year
18710921 Mechanotransduction in an extracted cell model: Fyn drives stretch- and flow-elicited PECAM-1 phosphorylation

Chiu, YJ, McBeath, E, Fujiwara, K

J Cell Biol 2008
16163360 A mechanosensory complex that mediates the endothelial cell response to fluid shear stress

Tzima, E, Irani-Tehrani, M, Kiosses, WB, Dejana, E, Schultz, DA, Engelhardt, B, Cao, G, DeLisser, H, Schwartz, MA

Nature 2005
25800053 Intramembrane binding of VE-cadherin to VEGFR2 and VEGFR3 assembles the endothelial mechanosensory complex

Coon, BG, Baeyens, N, Han, J, Budatha, M, Ross, TD, Fang, JS, Yun, S, Thomas, JL, Schwartz, MA

J Cell Biol 2015
Participants
Input
Output
Participates
as an event of
Catalyst Activity

protein tyrosine kinase activity of p-Y420-FYN [cytosol]

Physical Entity
p-Y420-FYN [cytosol] (Homo sapiens)
Activity
protein tyrosine kinase activity (GO:0004713)
Inferred From
Phosphorylation of Kdr and Flt4 in Pecam1:Cdh5:Kdr:Flt4:Ctnnb1 in response to shear stress (Mus musculus)
SRC phosphorylates PECAM1 (Bos taurus)
Authored
May, B  (2024-02-04)
Reviewed
Xiao, R  (2024-07-16)
Created
May, B  (2024-02-07)
Cite Us!