Prigent S A, Gullick W J
Molecular Oncology Laboratory, Hammersmith Hospital, London, UK.
EMBO J. 1994 Jun 15;13(12):2831-41. doi: 10.1002/j.1460-2075.1994.tb06577.x.
c-erbB-3 is a member of the type I (EGF receptor-related) family of growth factor receptors for which no ligand has been identified. To facilitate ligand stimulation we have constructed a chimeric receptor which possesses an activatable kinase and promotes the growth of NIH 3T3 fibroblasts. In this study we have shown that SHC and phosphatidylinositol 3'-kinase bind to the activated EGF receptor/c-erbB-3 chimera. Whereas p85 is not phosphorylated to a significant extent, SHC appears to be a major substrate for phosphorylation on tyrosine. In contrast to EGF receptor and c-erbB-2, we were unable to detect binding of activated c-erbB-3 to GRB2. Using synthetic peptides corresponding to each of 13 potential phosphorylation sites on c-erbB-3, we have shown that tyrosine 1309 is responsible for SHC binding. Peptides containing the motif YXXM inhibit p85 association. By comparison with recently reported SHC binding sites on Middle T antigen and Trk we have identified a SHC binding motif, NPXY.
c-erbB-3是I型（表皮生长因子受体相关）生长因子受体家族的成员，目前尚未发现其配体。为了便于配体刺激，我们构建了一种嵌合受体，它具有可激活的激酶并能促进NIH 3T3成纤维细胞的生长。在本研究中，我们发现SHC和磷脂酰肌醇3'-激酶与激活的表皮生长因子受体/c-erbB-3嵌合体结合。虽然p85没有明显的磷酸化，但SHC似乎是酪氨酸磷酸化的主要底物。与表皮生长因子受体和c-erbB-2不同，我们未能检测到激活的c-erbB-3与GRB2的结合。使用与c-erbB-3上13个潜在磷酸化位点对应的合成肽，我们发现酪氨酸1309负责SHC的结合。含有YXXM基序的肽抑制p85的结合。通过与最近报道的中T抗原和Trk上的SHC结合位点进行比较，我们确定了一个SHC结合基序NPXY。
