Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 478

9.5.3.3 I-Peptide Receptor

Endothelial cells express carbohydrate I-peptide receptor (IPR) that is responsible
for lung colonization of cancer cells [ 884 ]. Receptor IPR corresponds to alterna-
tively spliced variants of Arg/Ser-rich splicing factors (SFRS1, SFRS2, SFRS5,
and SFRS7). Like many carbohydrate-binding proteins of the C-type lectin family,
SFRS protein that is not a C-type lectin requires calcium to bind to carbohydrates,
especially fucosylated oligosaccharides.

9.5.3.4 FGFRs

Fibroblast growth factor FGF2 provokes endothelial cell migration and angiogenesis
via 2 types of receptors: high-affinity receptor protein Tyr kinases such as FGFR1
and heparan sulfate proteoglycans such as transmembrane syndecan-4, a FGFR1
coreceptor. The latter determines the kinetics and magnitude of FGF2-induced
MAPK signaling (ERK1 and ERK2) by promoting the macropinocytosis of the
FGFR1-syndecan-4-FGF2 complex using RhoG and Rab5 GTPases [ 885 ]. Small
RhoG GTPase promotes membrane ruffling and macropinocytosis. Monomeric
Rab5 GTPase is involved in early signaling endosomes. Signaling from FGFR1
initiates MAPK activation; syndecan-4-dependent FGFR1 macropinocytosis modu-
lates the kinetics of MAPK activation.

9.5.3.5 VEGFRs

Angiogenic vascular endothelial growth factor VEGFa is also a potent vascular
permeabilizing factor, whereas endothelial growth factors, such as FGF2 and PDGF,
do not affect vascular permeability.
The VEGFR receptors participate in signaling pathways that control and
coordinate transcriptional, post-transcriptional, and post-translational mechanisms
involved in the control of endothelial cell behavior during angiogenic sprouting,
branching with endothelial leading tip and trailing stalk cells , and tubulogenesis.
Stalk cells support the extension of sprouting vessels, generate the trunk of new
vessels, build a vascular lumen in growing vessels, and maintain connection with
the parental vessel.
During angiogenesis, signaling launched by pro-angiogenic ligands (i.e.,
autocrine VEGFa and VEGFc regulators) of VEGFR2 and VEGFR3 select tip
cells for sprouting [ 886 ]. Angiogenic sprouting is guided by gradients of pro-
angiogenic growth factors and various guidance cues, such as semaphorins and
ephrins. The navigators Uncoordinated-5 homolog Unc5b (receptor of secreted
netrins), Roundabout homolog Robo4, plexin-D1, neuropilins, ephrin-B2, and
EPHb4 receptor are major conductors of angiogenesis.