Increased mitogenicity of an αβ heterodimeric PDGF receptor complex correlates with lack of RasGAP binding
Increased mitogenicity of an αβ heterodimeric PDGF receptor complex correlates with lack of RasGAP binding
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DOI：
10.1038/sj.onc.1202606
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发表时间：
1999-04-15
期刊：
影响因子：
8
通讯作者：
Rönnstrand, L
中科院分区：
文献类型：
--
作者：
Ekman, S;Thuresson, ER;Rönnstrand, L
不同的血小板衍生生长因子（PDGF）同种型通过二聚化、受体的同源二聚化以及异源二聚化引起其α和β蛋白酪氨酸激酶受体的活化。先前已经显示，异二聚体受体复合物介导比同二聚体复合物中的任一种更强的促有丝分裂应答。在这份报告中，我表明，在表达PDGF α和β受体的细胞中，PDGF-AB刺激，导致优先异源二聚体形成，导致β受体中Tyr 771的磷酸化程度非常低。相比之下，Tyr 771在β-受体的同源二聚体复合物中被磷酸化。磷酸化Tyr 771是RasGAP的结合位点;在缺乏与RasGAP结合能力的α-受体中不存在类似位点。异二聚体受体复合物中Tyr 771磷酸化的降低与RasGAP结合的降低相关，以及与Ras和MAP激酶的更有效活化相关，这与PDGF-AB引起的促有丝分裂性的增加一致，与PDGF-AA或PDGF-BB相比。
The different platelet-derived growth factor (PDGF) isoforms cause activation of their alpha and beta protein tyrosine kinase receptors through dimerization, Homodimerization as well as heterodimerization of receptors occur. It has been shown previously that the heterodimeric receptor complex mediates a stronger mitogenic response than either of the homodimeric complexes. In this report, me show that in cells expressing both PDGF alpha- and beta-receptors, stimulation with PDGF-AB, which leads to preferential heterodimer formation, leads to a very low degree of phosphorylation of Tyr771 in the beta-receptor. In contrast, Tyr771 is phosphorylated in a homodimeric complex of beta-receptors. Phosphorylated Tyr771 is a binding site for RasGAP; an analogous site is not present in the alpha-receptor, which lacks the ability to associate with RasGAP, The lowered phosphorylation of Tyr771 in the heterodimeric receptor complex correlates with lowered association with RasGAP, as well as with a more efficient activation of Ras and MAP kinase, which is consistent with the increased mitogenicity elicited by PDGF-AB, compared to PDGF-AA or PDGF-BB.