VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cells

Vascular endothelial growth factor receptors in the regulation of angiogenesis and lymphangiogenesis

“…Activation of the p42/44 MAP kinase pathway by VEGF and subsequent cell proliferation has been documented for many types of endothelial cells (Seetharam et al, 1995;D'Angelo et al, 1995;Rousseau et al, 1997;Kroll and Waltenberger, 1997;Takahashi and Shibuya, 1997;Landgren et al, 1998;Takahashi et al, 1999). Association of VEGFR-2 with Grb2 suggests that activated Ras might be involved in the regulation of the VEGF-induced mitogenic response.…”

“…Association of VEGFR-2 with Grb2 suggests that activated Ras might be involved in the regulation of the VEGF-induced mitogenic response. However, it was reported recently that in liver sinusoidal endothelial cells the VEGF growth signal is transduced mostly through PLCg-PKC and not via Ras (Takahashi et al, 1999). Phosphorylated VEGFR-2 rapidly recruits and activates PLCg (Waltenberger et al, 1994;D'Angelo et al, 1995;Guo et al, 1995;Xia et al, 1996;Takahashi and Shibuya, 1997) which then hydrolyses a cell membrane phospholipid, phosphatidyl inositol 4,5-bisphosphate, and releases sn-1,2-diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3).…”

“…These two second messengers are responsible for direct activation of certain PKC isoforms and for the release of Ca 2+ from intracellular stores, respectively (Criscuolo et al, 1989;Brock et al, 1991;de Vries et al, 1992). VEGF has been shown to selectively activate the Ca 2+ -sensitive PKC isoforms g and b2 in bovine aortic endothelial cells (Xia et al, 1996;Takahashi et al, 1999) and PKCe in HUVE cells (Wu et al, 2000). In the former case the mitogenic e ect of VEGF in endothelial cells was suppressed by PKC-b and -gselective inhibitors.…”

Regulation of VEGF-A Expression in Endothelial Cells by Transcriptional Gene Activation or Transcriptional Gene Silencing: Analysis of Genome Wide Transcriptional Response

“…VEGFR-2 seems to be the major mediator of angiogenesis and vascularization [16], whereas VEGFR-1 has been suggested to negatively regulate angiogenesis during embryogenesis, and positively in adulthood [17]. VEGF-A induces autophosphorylation of VEGFR-2, after which PLCγ binds to VEGFR-2, activating the MAPK/ERK cascade and proliferation of endothelial cells [18]. VEGF-A also activates other signaling pathways, such as Akt/PI3K [18].…”

High efficient adenoviral-mediated VEGF and Ang-1 gene delivery into osteogenically differentiated human mesenchymal stem cells

“…One of the most widely used growth factors to accomplish therapeutic angiogenesis is VEGF, an endothelial cell specific mitogen and survival factor (Takahashi et al, 1999;Gerber et al, 1998). It was shown that gene transfer of VEGF expression plasmids induced neovascularization and brought significant increased blood flow with restored vasomotion in collateral vessels (Bauters et al, 1994;Asahara et al, 1996) as well as at the microvascular level (Takeshita et al, 1998).…”