Figure 1: VEGF induces growth factor signalling that is dependent on PKARIα oxidation.

(a) PKARIα disulphide dimerization increased in a concentration-dependent manner in BAECs treated with either H₂O₂ or VEGF (n=3). In addition, H₂O₂ also induced a concentration-dependent increase in ERK phosphorylation, mimicking the effects of VEGF on growth factor signalling (n=3). (b) Increased ERK phosphorylation in BAECs stimulated with VEGF was attenuated by the PKA selective inhibitor Rp-8-Br-cAMPs (Rp-cAMPs) but not the adenylate cyclase inhibitor DDA (n=5). Neither inhibitor modulated VEGF-stimulated p38 mitogen-activated protein kinase phosphorylation. (c) The phosphorylation of CREB in BAECs stimulated by VEGF was attenuated by the PKA inhibitor Rp-8-Br-cAMPs (Rp-cAMPs) but not the adenylate cyclase inhibitor DDA (n=5). (d) Expression of S838A mutated KSR1 decreased VEGF-dependent ERK phosphorylation compared with WT (n=3) (e) Migration of BAEC by VEGF was partially attenuated by the PKA-specific inhibitor Rp-8-Br-cAMPs but not the adenylate cyclase inhibitor DDA (n=3). Data are shown as the mean±s.e.m. *P<0.05, **P<0.01 determined by t-test.