Placenta growth factor stimulates MAP kinase and mitogenicity but not phospholipase C-γ and migration of endothelial cells expressing Flt 1
Placenta growth factor stimulates MAP kinase and mitogenicity but not phospholipase C-γ and migration of endothelial cells expressing Flt 1
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DOI：
10.1038/sj.onc.1201545
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发表时间：
1998-01-22
期刊：
影响因子：
8
通讯作者：
Claesson-Welsh, L
中科院分区：
文献类型：
--
作者：
Landgren, E;Schiller, P;Claesson-Welsh, L
血管内皮生长因子（VEGF）和胎盘生长因子（PlGF）是结构上相关的内皮细胞生长因子。VEGF以高亲和力结合相关受体酪氨酸激酶Flt 1和KDR/Flk 1，而PlGF仅结合Flt 1。已知配体刺激的KDR抑制细胞活性（如增殖和迁移）的信号，而对于Fit 1已经记录到弱响应或没有响应。我们研究了VEGF和PIGF刺激表达Fit 1或KDR的猪主动脉内皮细胞中信号转导的能力。VEGF对表达Flt 1的细胞基本上没有影响，但诱导表达KDR的细胞的DNA合成和迁移。另一方面，PlGF诱导DNA合成，但不诱导Fit 1细胞的迁移。在协议中，MAP激酶，检查作为DNA合成的标志物，被激活的VEGF刺激的KDR细胞和PlGF刺激的Fit 1细胞。相比之下，磷脂酶C-γ（PLC-γ）仅在VEGF刺激的KDR细胞中酪氨酸磷酸化，而在PlGF刺激的Fit 1细胞中不酪氨酸磷酸化，这与PLC-γ在细胞迁移中的作用一致。我们还检查了纤溶酶原激活物（PA）的蛋白水平的诱导，这在PlGF刺激的Fit 1细胞中是明显的，但在VEGF刺激的KDR细胞中不是。这些数据表明，当适当刺激时，Fit 1能够介导一系列生物信号，并且Fit 1的PlGF刺激的响应模式与KDR的VEGF刺激的响应模式不同。
Vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) are structurally related growth factors for endothelial cells. VEGF binds to the related receptor tyrosine kinases Fit 1 and KDR/Flk 1 with high affinity, whereas PlGF binds only to Fit 1. Ligand-stimulated KDR is known to transduce signals for cellular activity such as proliferation and migration, whereas weak or no responses have been recorded for Fit 1. We examined VEGF and PIGF for their capacity to stimulate signal transduction in porcine aortic endothelial cells expressing Fit 1 or KDR. VEGF had essentially no effect on Fit 1 expressing cells, but induced DNA synthesis and migration of KDR expressing cells. PlGF on the other hand induced DNA synthesis but not migration of the Fit 1 cells. In agreement, MAP kinase, examined as a marker for DNA synthesis, was activated both by VEGF-stimulation of the KDR cells and by PlGF-stimulation of the Fit 1 cells. In contrast, phospholipase C-gamma (PLC-gamma), was tyrosine phosphorylated only in VEGF stimulated KDR cells, and not in the PlGF-stimulated Fit 1 cells, which is in agreement with a role for PLC-gamma in cellular migration. We furthermore examined induction of protein levels of plasminogen activator (PA), which was evident in the PlGF-stimulated Fit 1 cells, but not in the VEGF-stimulated KDR cells. These data show that Fit 1 is able to mediate an array-of biological signals when appropriately stimulated and that the pattern of responses of PlGF-stimulation of Fit 1 is distinct from the pattern of responses to VEGF-stimulation of KDR.