Signaling properties of VEGF receptor-1 and-2 homo- and heterodimers
Signaling properties of VEGF receptor-1 and-2 homo- and heterodimers
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DOI：
10.1016/s1357-2725(01)00019-x
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发表时间：
2001-04-01
影响因子：
4
通讯作者：
Claesson-Welsh, L
中科院分区：
文献类型：
--
作者：
Huang, K;Andersson, C;Claesson-Welsh, L
血管内皮生长因子（VEGF-A）通过受体酪氨酸激酶VEGF受体-1（VEGFR-1）和VEGFR-2发挥其作用，所述受体酪氨酸激酶在体外和体内在大多数内皮细胞类型上表达。我们研究了VEGF-A诱导的猪主动脉内皮细胞（PAE）单独表达VEGFR-1或VEGFR-2，细胞共表达两种受体类型的信号转导。我们发现，VEGF-A刺激的PAE细胞共表达VEGFR-1和-2含有受体异源二聚体。所有三种细胞系（表达VEGFR-1、-2和-1/2）的VEGF-A刺激导致具有不同效率的信号转导。因此，磷脂酶Cy的酪氨酸磷酸化和肌醇多磷酸的积累在VEGFR-1/2细胞中被有效地转导，而表达VEGFR-1的细胞在这些测定中反应较差。相比之下，VEGF-A诱导的磷酸肌醇3-激酶的激活和Ca 2+通量的诱导被VEGFR-1和VEGFR-2同源二聚体和异源二聚体很好地转导。Ca 2+通量的模式是独特的每种类型的VEGF受体二聚体。我们的数据表明，由VEGF-A诱导的信号转导是由VEGF受体的同源二聚体和异源二聚体以不同的方式转导。(C)2001爱思唯尔科技有限公司版权所有。
Vascular endothelial growth factor (VEGF-A) exerts its effects through receptor tyrosine kinases VEGF receptor-1 (VEGFR-1) and VEGFR-2, which are expressed on most endothelial cell types in vitro and in vivo. We have examined VEGF-A-induced signal transduction in porcine aortic endothelial (PAE) cells individually expressing VEGFR-1 or VEGFR-2, and cells co-expressing both receptor types. We show that VEGF-A-stimulated PAE cells co-expressing VEGFR-1 and -2 contain receptor heterodimers. VEGF-A-stimulation of all three cell lines (expressing VEGFR-1, -2 and -1/2) resulted in signal transduction with different efficiencies. Thus, tyrosine phosphorylation of phospholipase Cy, and accumulation of inositol polyphosphates were efficiently transduced in the VEGFR-1/2 cells whereas cells expressing VEGFR-1 responded poorly in these assays. In contrast, VEGF-A-induced activation of phosphoinositide 3-kinase and induction of Ca2+ fluxes were transduced well by VEGFR-1 and VEGFR-2 homo- and heterodimers. The pattern of Ca2+ fluxes was unique for each type of VEGF receptor dimer. Our data show that signal transduction induced by VEGF-A is transduced in distinct manners by homo- and heterodimers of VEGF receptors. (C) 2001 Elsevier Science Ltd. All rights reserved.