Journal article

Publication year: 2011

Pages: 1819-1830

Journal: Journal of Cell Science

Volume number: 124

Issue number: 11

ISSN: 0021-9533

eISSN: 1477-9137

DOI Link: https://doi.org/10.1242/jcs.077594

Publisher: The Company of Biologists

Abstract: 
VEGF-, phosphoinositide 3-kinase (PI3K)- and protein kinase C (PKC)-regulated signaling in cardiac and vascular differentiation was investigated in mouse ES cells and in ES cell-derived Flk-1(+) cardiovascular progenitor cells. Inhibition of PI3K by wortmannin and LY294002, disruption of PI3K catalytic subunits p110 alpha and p110 delta using short hairpin RNA (shRNA), or inhibition of p110 alpha with compound 15e and of p110 delta with IC-87114 impaired cardiac and vascular differentiation. By contrast, TGX-221, an inhibitor of p110 beta, and shRNA knockdown of p110 beta were without significant effects. Antagonists of the PKC family, i.e. bisindolylmaleimide-1 (BIM-1), G 6976 (targeting PKC alpha/beta II) and rottlerin (targeting PKC delta) abolished vasculogenesis, but not cardiomyogenesis. Inhibition of Akt blunted cardiac as well as vascular differentiation. VEGF induced phosphorylation of PKC alpha/beta II and PKC delta but not PKC zeta. This was abolished by PI3K inhibitors and the VEGFR-2 antagonist SU5614. Furthermore, phosphorylation of Akt and phosphoinositide-dependent kinase-1 (PDK1) was blunted upon inhibition of PI3K, but not upon inhibition of PKC by BIM-1, suggesting that activation of Akt and PDK1 by VEGF required PI3K but not PKC. In summary, we demonstrate that PI3K catalytic subunits p110 alpha and p110 delta are central to cardiovasculogenesis of ES cells. Akt downstream of PI3K is involved in both cardiomyogenesis and vasculogenesis, whereas PKC is involved only in vasculogenesis.

Harvard Citation style: Bekhite, M., Finkensieper, A., Binas, S., Mueller, J., Wetzker, R., Figulla, H., et al. (2011) VEGF-mediated PI3K class IA and PKC signaling in cardiomyogenesis and vasculogenesis of mouse embryonic stem cells, Journal of Cell Science, 124(11), pp. 1819-1830. https://doi.org/10.1242/jcs.077594

APA Citation style: Bekhite, M., Finkensieper, A., Binas, S., Mueller, J., Wetzker, R., Figulla, H., Sauer, H., & Wartenberg, M. (2011). VEGF-mediated PI3K class IA and PKC signaling in cardiomyogenesis and vasculogenesis of mouse embryonic stem cells. Journal of Cell Science. 124(11), 1819-1830. https://doi.org/10.1242/jcs.077594