Arvidsson A K, Heldin C H, Claesson-Welsh L
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Cell Growth Differ. 1992 Dec;3(12):881-7.
The platelet-derived growth factor (PDGF) alpha- and beta-receptors both mediate a mitogenic response, but only the beta-receptor mediates circular actin reorganization and chemotaxis. The tyrosine kinase domains of the receptors contain noncatalytic inserts of about 100 residues. In order to determine the role of these domains in the differential signaling of the two receptors, we constructed chimeric PDGF receptors and expressed the constructs in porcine aortic endothelial cells. The chimeric receptors were similar to the wild-type receptors in their ability to induce mitogenicity in response to ligand. Examination of receptor-associated substrates by in vitro kinase assays revealed that phosphoproteins of 72 and 110 kilodaltons were associated with the kinase insert of the alpha-receptor, whereas a phosphoprotein of 130 kilodaltons was associated with the kinase insert of the beta-receptor. Actin reorganization in the form of circular membrane ruffling was seen after ligand stimulation of the beta-receptor and the alpha-receptor containing the beta-receptor kinase insert but not after stimulation of the alpha-receptor or the beta-receptor containing the alpha-receptor kinase insert. These data indicate that the PDGF beta-receptor kinase insert has an essential function in the signal transduction pathway leading to circular membrane ruffling.
血小板衍生生长因子（PDGF）的α受体和β受体都能介导促有丝分裂反应，但只有β受体能介导环状肌动蛋白重组和趋化作用。受体的酪氨酸激酶结构域包含约100个残基的非催化插入片段。为了确定这些结构域在两种受体差异信号传导中的作用，我们构建了嵌合型PDGF受体，并在猪主动脉内皮细胞中表达这些构建体。嵌合受体在响应配体诱导有丝分裂的能力方面与野生型受体相似。通过体外激酶分析检测受体相关底物发现，72千道尔顿和110千道尔顿的磷蛋白与α受体的激酶插入片段相关，而130千道尔顿的磷蛋白与β受体的激酶插入片段相关。在配体刺激β受体和含有β受体激酶插入片段的α受体后，可见以环状膜皱褶形式出现的肌动蛋白重组，但在刺激α受体或含有α受体激酶插入片段的β受体后则未见到。这些数据表明，PDGFβ受体激酶插入片段在导致环状膜皱褶的信号转导途径中具有重要功能。
