Priming of the vascular endothelial growth factor signaling pathway by thrombospondin-1, CD36, and spleen tyrosine kinase
Priming of the vascular endothelial growth factor signaling pathway by thrombospondin-1, CD36, and spleen tyrosine kinase
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DOI：
10.1182/blood-2010-09-305284
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发表时间：
2011-04-28
期刊：
影响因子：
20.3
通讯作者：
Lawler, Jack
中科院分区：
文献类型：
--
作者：
Kazerounian, Shideh;Duquette, Mark;Lawler, Jack
CD 36通过与血小板反应蛋白-1（TSP-1）的1型重复序列结合并激活Fyn酪氨酸激酶和MAPK途径在抑制血管生成中起关键作用。在这里，我们揭示了一种新的协会CD 36与VEGFR-2和脾酪氨酸激酶（Syk）。我们还通过证明CD 36在HUVECs中的过表达上调内源性Syk表达来解决CD 36和Syk表达之间的相关性。我们还定义了一个新的作用，TSP-1和CD 36在活化的VEGFR-2信号通路，需要Syk。我们的研究结果还确定了Syk作为VEGF-A诱导的血管生成的刺激物的作用，通过增加VEGFR-2中Y1175的磷酸化，这是促进VEGF-A诱导的内皮细胞迁移的主要酪氨酸。总之，这些研究为TSP-1，CD 36和Syk引入了一种新的信号通路，并解决了这些蛋白在调节血管生成开关中的作用。（血。2011;117（17）：4658-4666）
CD36 plays a critical role in the inhibition of angiogenesis through binding to the type 1 repeats of thrombospondin-1 (TSP-1) and activating Fyn tyrosine kinase and MAPK pathways. Here, we reveal a novel association of CD36 with VEGFR-2 and spleen tyrosine kinase (Syk). We also address the correlation between the expression of CD36 and Syk by demonstrating that overexpression of CD36 in HUVECs up-regulates endogenous Syk expression. We also define a new role for TSP-1 and CD36 in the activation of the VEGFR-2 signaling pathway that requires Syk. Our findings also identify a role for Syk as a stimulator of VEGF-A-induced angiogenesis by increasing phosphorylation of Y1175 in VEGFR-2, which is a major tyrosine for promoting VEGF-A-induced endothelial cell migration. Together, these studies introduce a new signaling pathway for TSP-1, CD36, and Syk, and address the role of these proteins in regulating the angiogenic switch.(Blood. 2011;117(17):4658-4666)