Hooshmand-Rad R, Yokote K, Heldin C H, Claesson-Welsh L
Ludwig Institute for Cancer Research, Box 595, Biomedical Center, S-751 24 Uppsala, Sweden.
J Cell Sci. 1998 Mar;111 ( Pt 5):607-14. doi: 10.1242/jcs.111.5.607.
Two novel autophosphorylation sites in the juxtamembrane region of the PDGF alpha-receptor, Tyr-572 and Tyr-574, were identified. A Y572/574F mutant PDGF (alpha)-receptor was generated and stably expressed in porcine aortic endothelial cells. In contrast to the wild-type receptor, the mutant receptor was unable to associate with or activate Src family tyrosine kinases. Tyrosine phosphorylated synthetic peptides representing the juxtamembrane sequence of the receptor dose-dependently inhibited the binding of Src family tyrosine kinases to the autophosphorylated PDGF alpha-receptor. The mutant receptor showed similar PDGF-induced kinase activity and ability to mediate mitogenicity, actin reorganization and chemotaxis as the wild-type receptor. Thus activation of Src family kinases by the PDGF alpha-receptor is not essential for PDGF-induced mitogenicity or actin reorganization.
在血小板衍生生长因子α受体（PDGFα受体）近膜区域鉴定出两个新的自磷酸化位点，即酪氨酸-572（Tyr-572）和酪氨酸-574（Tyr-574）。构建了Y572/574F突变型PDGF（α）受体，并在猪主动脉内皮细胞中稳定表达。与野生型受体不同，突变型受体无法与Src家族酪氨酸激酶结合或激活它们。代表受体近膜序列的酪氨酸磷酸化合成肽呈剂量依赖性地抑制Src家族酪氨酸激酶与自磷酸化的PDGFα受体的结合。突变型受体表现出与野生型受体相似的PDGF诱导的激酶活性以及介导有丝分裂、肌动蛋白重组和趋化性的能力。因此，PDGFα受体对Src家族激酶的激活对于PDGF诱导的有丝分裂或肌动蛋白重组并非必不可少。
