REGULATION OF CHEMOTAXIS BY THE PLATELET-DERIVED GROWTH-FACTOR RECEPTOR-BETA
REGULATION OF CHEMOTAXIS BY THE PLATELET-DERIVED GROWTH-FACTOR RECEPTOR-BETA
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DOI：
10.1038/367474a0
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发表时间：
1994-02-03
期刊：
影响因子：
64.8
通讯作者：
ZETTER, BR
中科院分区：
文献类型：
--
作者：
KUNDRA, V;ESCOBEDO, JA;ZETTER, BR
趋化性是伤口愈合、发育、免疫和转移的重要组成部分，但介导趋化性的信号通路却知之甚少。血小板衍生生长因子 (PDGF) 既可作为有丝分裂原，又可作为化学引诱剂1。受到刺激后，酪氨酸激酶 PDGF 受体-β (PDGFR-β) 会自动磷酸化 2 并形成复合物，其中包括含有 SH2（Src 同源性 2）结构域的蛋白质，例如磷脂酰肌醇特异性磷脂酶 C-gamma（参考文献 3）、Ras-GTP 酶激活蛋白 (GAP)4 和磷脂酰肌醇-3-OH 激酶 5。 PDGFR-β 中特定的酪氨酸至苯丙氨酸取代可以阻止一种含有 SH2 结构域的蛋白质的结合，而不影响其他受体相关蛋白质的结合 6,7。在这里，我们使用磷脂酶 C-gamma（参考文献 8）和 PDGFR-beta 突变体 9-11 来绘制参与 PDGF-BB 同二聚体趋化性正向和负向调节的特定酪氨酸。我们的结果表明，PDGFR-β 招募迁移促进（磷脂酶 C-gamma 和磷脂酰肌醇-3-OH 激酶）和迁移抑制 (GAP) 活性之间的微妙平衡，以驱动 PDGF-BB 的趋化性。
CHEMOTAXIS is an important component of wound healing, development, immunity and metastasis, yet the signalling pathways that mediate chemotaxis are poorly understood. Platelet-derived growth factor (PDGF) acts both as a mitogen and a chemoattractant1. Upon stimulation, the tyrosine kinase PDGF receptor-beta (PDGFR-beta) autophosphorylates2 and forms a complex that includes SH2(Src homology 2)-domain-containing proteins such as the phosphatidylinositol-specific phospholipase C-gamma (ref. 3), Ras-GTPase-activating protein (GAP)4, and phosphatidylinositol-3-OH kinase5. Specific tyrosine-to-phenylalanine substitutions in the PDGFR-beta can prevent binding of one SH2-domain-containing protein without affecting binding of other receptor-associated proteins6,7. Here we use phospholipase C-gamma (ref. 8) and PDGFR-beta mutants9-11 to map specific tyrosines involved in both positive and negative regulation of chemotaxis towards the PDGF-BB homodimer. Our results indicate that a delicate balance of migration-promoting (phospholipase C-gamma and phosphatidylinositol-3-OH kinase) and migration-suppressing (GAP) activities are recruited by the PDGFR-beta to drive chemotaxis towards PDGF-BB.