VEGF signaling, mTOR complexes, and the endoplasmic reticulum: Towards a role of metabolic sensing in the regulation of angiogenesis.
Vascular endothelial growth factor (VEGF) activates unfolded protein response sensors in the endoplasmic reticulum through phospholipase C gamma (PLCγ)-mediated crosstalk with mammalian target of rapamycin complex 1 (mTORC1). Activation of transcription factor 6 (ATF6) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) activate mTORC2, ensuring maximal endothelial cell survival and angiogenic activity through phosphorylation of AKT on Ser473. As mTORC1 is a metabolic sensor, metabolic signals may be integrated with signals from VEGF in the regulation of angiogenesis.
Foundation of Research and Technology-Hellas; Institute of Molecular Biology & Biotechnology - Department of Biomedical Research; Ioannina, Greece; Laboratory of Biological Chemistry; Medical School; University of Ioannina; Ioannina, Greece.
Evdoxia
E
Karali
Foundation of Research and Technology-Hellas; Institute of Molecular Biology & Biotechnology - Department of Biomedical Research; Ioannina, Greece; Department of Informatics and Telecommunications Engineering; University of Western Macedonia; Kozani, Greece.
Sofia
S
Bellou
Department of Cancer Biology; Biomedical Research Foundation of the Academy of Athens ; Athens, Greece.
Dimitris
D
Stellas
Department of Cancer Biology; Biomedical Research Foundation of the Academy of Athens ; Athens, Greece.
Apostolos
A
Klinakis
Foundation of Research and Technology-Hellas; Institute of Molecular Biology & Biotechnology - Department of Biomedical Research ; Ioannina, Greece.
Carol
C
Murphy
Foundation of Research and Technology-Hellas; Institute of Molecular Biology & Biotechnology - Department of Biomedical Research; Ioannina, Greece; Laboratory of Biological Chemistry; Medical School; University of Ioannina; Ioannina, Greece.
Theodore
T
Fotsis
AKT; ATF6; CHOP; IRE1α; PERK; PLCγ; VEGF; angiogenesis; apoptosis; mTORC1; mTORC2; survival; unfolded protein response