Extracellular Purines in Endothelial Cell Barrier Regulation - Extracellular ATP and Adenosine as Regulators of Endothelial Cell Function - page 41

Fig. 3.1 Purinoceptor-activated cell signaling pathways, which affect barrier function of
endothelial monolayers (see also explanations in the text). Pathways leading to enhancement of
endothelial integrity are shown in red. Barrier-disruptive pathways are shown in black

α

to G i protein-mediated signaling is activation of Src kinase [61, 93]. In EC, Src

kinase positively regulates caveolae-mediated transcytosis of albumin by phospho-
rylation of caveolin-1, gp60 and dynamin-2 [92, 96]. Phosphorylation of dynamin-2
can also stimulate clathrin- and caveolin-dependent endocytosis, and, therefore,
enhance internalization of transmembrane proteins involved in cell-cell contacts.
Activated Src may initiate transactivation of receptor tyrosine kinases (RTK) and
RTK-mediated signaling.
Gq/11 protein-mediated signaling is activated by agonist stimulation of A2B,
P2Y1, P2Y2, P2Y4, P2Y6 and P2Y11 receptors [21, 22, 36, 37, 65, 81, 105].
Dissociated G and positively

modulate production of IP 3 and DAG [78]. This, in turn, leads to [Ca 2+ ] i influx
and activation of PKC isoforms [73]. Extensive studies performed in EC have

α qorG α 11 subunits directly interact with PLC β