Purinergic regulation of vascular endothelial growth factor signaling in angiogenesis.
Purinergic regulation of vascular endothelial growth factor signaling in angiogenesis.
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DOI：
10.1038/sj.bjc.6604998
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发表时间：
2009-05-05
影响因子：
8.8
通讯作者：
Buxton, I. L. O.
中科院分区：
文献类型：
--
作者：
Rumjahn, S. M.;Yokdang, N.;Baldwin, K. A.;Thai, J.;Buxton, I. L. O.
P2 Y嘌呤核苷酸受体（P2 YRs）通过乳腺癌细胞分泌的核苷二磷酸激酶（NDPK）促进内皮细胞小管形成。我们检验了激活的P2 Y1受体在血管生成信号传导中反式激活血管内皮生长因子受体（VEGFR-2）的假设。血管生成的P2 Y1 R刺激（10 μM 2-甲硫基-ATP（2 MS-ATP））被VEGFR-2酪氨酸激酶抑制剂SU 1498（1 μM）抑制。0.0262或2.62 nM VEGF对VEGFR-2的磷酸化作用与0.01或10 μM 2 MS-ATP对P2 Y1 R的刺激相当。2 MS-ATP和VEGF刺激增加了tyr 1175处的酪氨酸磷酸化。2 MS-ATP（0.1-10 μM）也以剂量依赖性方式促进EC小管形成。在2 MS-ATP浓度增加的情况下，加入次最大VEGF（70 pM）在2 MS-ATP浓度<3 μM时产生累加效应，而在2 MS-ATP浓度<3 μM时产生饱和效应和小于累加效应。我们提出，VEGF受体可以在没有VEGF的情况下被激活，并且P2 YR-VEGFR 2相互作用和由此产生的信号转导是血管稳态和肿瘤介导的血管生成的关键决定因素。
P2Y purine nucleotide receptors (P2YRs) promote endothelial cell tubulogenesis through breast cancer cell-secreted nucleoside diphosphate kinase (NDPK). We tested the hypothesis that activated P2Y1 receptors transactivate vascular endothelial growth factor receptor (VEGFR-2) in angiogenic signaling. P2Y1R stimulation (10 μM 2-methyl-thio-ATP (2MS-ATP)) of angiogenesis is suppressed by the VEGFR-2 tyrosine kinase inhibitor, SU1498 (1 μM). Phosphorylation of VEGFR-2 by 0.0262 or 2.62 nM VEGF was comparable with 0.01 or 10 μM 2MS-ATP stimulation of the P2Y1R. 2MS-ATP, and VEGF stimulation increased tyrosine phosphorylation at tyr1175. 2MS-ATP (0.1–10 μM) also stimulated EC tubulogenesis in a dose-dependent manner. The addition of sub-maximal VEGF (70 pM) in the presence of increasing concentrations of 2MS-ATP yielded additive effects at 2MS-ATP concentrations <3 μM, whereas producing saturated and less than additive effects at ⩾3 μM. We propose that the VEGF receptor can be activated in the absence of VEGF, and that the P2YR–VEGFR2 interaction and resulting signal transduction is a critical determinant of vascular homoeostasis and tumour-mediated angiogenesis.
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影响因子：
8.8
作者：
Rumjahn, S M;Javed, M A;Wong, N;Law, W E;Buxton, I L O
通讯作者：
Buxton, I L O
影响因子：
6.7
作者：
Kaczmarek, E;Erb, L;Robson, SC
通讯作者：
Robson, SC
DOI：
10.1073/pnas.0404984102
发表时间：
2005-01-25
影响因子：
11.1
作者：
Sakurai, Y;Ohgimoto, K;Shibuya, M
通讯作者：
Shibuya, M
影响因子：
3.5
作者：
Tanaka, N;Kawasaki, K;Shinozuka, K
通讯作者：
Shinozuka, K
影响因子：
4.8
作者：
Holmqvist, K;Cross, MJ;Welsh, M
通讯作者：
Welsh, M