Abstract:KDR/Flk-1 tyrosine kinase, one of the two receptors for Vascular Endothelial Growth Factor (VEGF) has been shown to generate the major part of mitotic signals in endothelial cells, although the mechanisms are poorly understood. Here we examined the processing and signal transduction of KDR/Flk-1. Both in endothelial cells and in NIH3T3 cells expressing KDR/Flk-1, an immature form of KDR/Flk-1 with a molecular mass of about 150 kDa was glycosylated to create a 200 kDa intermediate, and after further glycosylati… Show more
“…However, ERK1/2 may not play a major role in this system, since speci®c inhibition of ERK1/2 by PD98059 exhibited only a marginal e ect on vinculin assembly and phosphorylation of FAK and paxillin. Previous reports indicate that VEGF, by binding to KDR, activates ERK1/2 via a phospholipase Cg (PLCg)-PKC-dependent pathway (Seetharam et al, 1995;Guo et al, 1995;Takahashi and Shibuya, 1997). We observed that speci®c inhibition of PKC by GF109203X completely abrogated vinculin assembly as well as DNA sysnthesis.…”
“…However, ERK1/2 may not play a major role in this system, since speci®c inhibition of ERK1/2 by PD98059 exhibited only a marginal e ect on vinculin assembly and phosphorylation of FAK and paxillin. Previous reports indicate that VEGF, by binding to KDR, activates ERK1/2 via a phospholipase Cg (PLCg)-PKC-dependent pathway (Seetharam et al, 1995;Guo et al, 1995;Takahashi and Shibuya, 1997). We observed that speci®c inhibition of PKC by GF109203X completely abrogated vinculin assembly as well as DNA sysnthesis.…”
“…Nonetheless, various lines of evidence in different tumor types suggest that the VEGF/VEGFR-2 system plays an important role in the regulation of tumor cell growth through the activation of the mitogen-activated protein kinase pathway and, subsequently, the mitogenic response. 56,57 It also is possible that, like endothelial cells, activity of the VEGF/VEGFR-2 system in craniopharyngiomas may be linked to the increasing permeability of epithelial cells and cyst formation. This signaling pathway provides an intriguing mechanism that may establish a direct correlation between VEGF expression and tumor cyst formation, as observed by Vaquero et al 22 in their study of craniopharyngiomas.…”
The functional single‐coordinate phosphine oxide ligands (4‐diphenylaminophenyl)diphenylphosphine oxide (TAPO), (4‐naphthalen‐1‐yl‐phenylaminophenyl)diphenylphosphine oxide (NaDAPO), and 9‐[4‐(diphenylphosphinoyl)phenyl]‐9H‐carbazole (CPPO), as the direct combinations of hole‐transporting moieties, and electron‐transporting triphenylphosphine oxide (TPPO) were designed and synthesized (amines or carbazole), together with their EuIII complexes [Eu(tapo)2(tta)3] (1), [Eu(nadapo)2(tta)3] (2), and [Eu(cppo)2(tta)3] (3; TTA: 2‐thenoyltrifluoroacetonate). The investigation indicated that by taking advantage of the modification inertia of the phosphine oxide ligands, the direct introduction of the hole‐transport groups as chromophore made TAPO, NaDAPO, and CPPO obtain the most compact structure and mezzo S1 and T1 energy levels, which improved the intramolecular energy transfer in their EuIII complexes. The amorphous phase of 1–3 proved the weak intermolecular interaction, which resulted in extraordinarily low self‐quenching of the complexes. The excellent double‐carrier transport ability of the ligands was studied with Gaussian calculations, and the bipolar structure of TAPO and CPPO was proved. The great improvement of the double‐carrier transport ability of 1–3 was shown by cyclic voltammetry. Their HOMO and LUMO energy levels of around 5.3 and 3.0 eV, respectively, are the best results for EuIII complexes reported so far. A single‐layer organic light‐emitting diode of 2 had the impressive brightness of 59 cd m−2 which, to the best of our knowledge, is the highest reported so far. Both of the four‐layer devices based on pure 1 and 2 had a maximum brightness of more than 1000 cd m−2, turn‐on voltages lower than 5 V, maximum external quantum yields of more than 3 % and excellent spectral stability.
“…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.…”
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