Mutation of a src phosphorylation site in the PDGF beta-receptor leads to increased PDGF-stimulated chemotaxis but decreased mitogenesis
Mutation of a src phosphorylation site in the PDGF beta-receptor leads to increased PDGF-stimulated chemotaxis but decreased mitogenesis
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DOI：
10.1002/j.1460-2075.1996.tb00915.x
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发表时间：
1996-10-01
期刊：
影响因子：
11.4
通讯作者：
Ronnstrand, L
中科院分区：
文献类型：
--
作者：
Hansen, K;Johnell, M;Ronnstrand, L
配体诱导的血小板衍生生长因子β受体(PDGF)的激活导致了Src家族酪氨酸激酶的激活。我们探索了受体本身是Src底物的可能性。我们发现，PDGF受体激动域中的Tyr934被Src磷酸化。表达β受体突变体的细胞系，其中的Tyr934被取代，苯丙氨酸残基，显示出对PDGF-BB的促有丝分裂信号。相反，突变体受体介导的趋化和肌动蛋白重组的信号增加，而表达野生型β受体的细胞的运动反应仅仅被磷脂酰肌醇3‘-激酶抑制而减弱。与野生型受体细胞相比，表达突变受体的细胞对PDGF-BB诱导的趋化作用的影响较小，而表达轻型β受体的细胞的趋化作用受到的影响较小。此外，与野生型受体细胞相比，突变受体细胞中PDGF-BB刺激的磷脂酶C-γ酪氨酸磷酸化增强。
Ligand induced activation of the beta-receptor for platelet-derived growth factor (PDGF) leads to activation of Src family tyrosine kinases, We have explored the possibility that the receptor itself is a substrate for Src, We show that Tyr934 in the kinase domain of the PDGF receptor is phosphorylated by Src, Cell lines expressing a beta-receptor mutant, in which Tyr934 was replaced,vith a phenyalanine residue, showed reduced mitogenic signaling in response to PDGF-BB, In contrast, the mutant receptor mediated increased signals for chemotaxis and actin reorganization, Whereas the motility responses of cells expressing wild-type beta-receptors mere attenuated by inhibition of phosphatidylinositol 3'-kinase, those of cells expressing the mutant receptor were only slightly influenced, In contrast, PDGF-BB-induced chemotaxis of the cells with the mutant receptor was attenuated by inhibition of protein kinase C, whereas the chemotaxis of cells expressing the mild-type beta-receptor was less affected, Moreover, the PDGF-BB-stimulated tyrosine phosphorylation of phospholipase C-gamma was increased in the mutant receptor cells compared with wild-type receptor cells, In conclusion, the characteristics of the Y934F mutant suggest that the phosphorylation of Tyr934 by Src negatively modulates a signal transduction pathway leading to motility responses which involves phospholipase C-gamma, and shifts the response to increased mitogenicity.