PKC? activation promotes FGF-2 exocytosis and induces endothelial cell proliferation and sprouting.

ABSTRACT: Protein kinase C epsilon (PKC?) activation controls fibroblast growth factor-2 (FGF-2) angiogenic signaling. Here, we examined the effect of activating PKC? on FGF-2 dependent vascular growth and endothelial activation. ??RACK, a selective PKC? agonist induces pro-angiogenic responses in endothelial cells, including formation of capillary like structures and cell growth. These effects are mediated by FGF-2 export to the cell membrane, as documented by biotinylation and immunofluorescence, and FGF-2/FGFR1 signaling activation, as attested by ERK1/2-STAT-3 phosphorylation and de novo FGF-2 synthesis. Similarly, vascular endothelial growth factor (VEGF) activates PKC? in endothelial cells, and promotes FGF-2 export and FGF-2/FGFR1 signaling activation. ??RACK fails to elicit responses in FGF-2(-/-) endothelial cells, and in cells pretreated with methylamine (MeNH2), an exocytosis inhibitor, indicating that both intracellular FGF-2 and its export toward the membrane are required for the ??RACK activity. In vivo ??RACK does not induce angiogenesis in the rabbit cornea. However, ??RACK promotes VEGF angiogenic responses, an effect sustained by endothelial FGF-2 release and synthesis, since anti-FGF-2 antibody strongly attenuates VEGF responses. The results demonstrate that PKC? stimulation promotes angiogenesis and modulates VEGF activity, by inducing FGF-2 release and autocrine signaling.

SUBMITTER: Monti M 

PROVIDER: S-EPMC3812807 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature