Barber D L, Corless C N, Xia K, Roberts T M, D'Andrea A D
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Blood. 1997 Jan 1;89(1):55-64.
Stimulation of the erythropoietin receptor (EPO-R) or the interleukin-2 receptor (IL-2-R) by their respective ligands has been reported to activate tyrosine phosphorylation of the cytoplasmic protein, Shc. We have recently characterized a cell line, CTLL-EPO-R, that contains functional cell-surface receptors for both EPO and IL-2. Although stimulation with IL-2 or IL-15 resulted in the rapid, dose-dependent tyrosine phosphorylation of Shc, stimulation with EPO failed to activate Shc. EPO, IL-2, and IL-15 activated the tyrosine phosphorylation of the adaptor protein, Shp2, and the association of Shp2/Grb2/cytokine receptor complexes. In addition, EPO, IL-2, and IL-15 activated Raf1 and ERK2, demonstrating that the Raf1/MEK/MAP kinase pathway was activated. These results indicate that multiple biochemical pathways are capable of conferring a mitogenic signal in CTLL-EPO-R. EPO can activate the Raf1/MEK/MAP kinase pathway via Shc-dependent or Shc-independent pathways, and Shc activation is not required for EPO-dependent cell growth in CTLL-EPO-R.
据报道，促红细胞生成素受体（EPO-R）或白细胞介素-2受体（IL-2-R）被其各自的配体刺激后会激活细胞质蛋白Shc的酪氨酸磷酸化。我们最近鉴定了一种细胞系CTLL-EPO-R，它含有EPO和IL-2的功能性细胞表面受体。尽管用IL-2或IL-15刺激会导致Shc迅速发生剂量依赖性酪氨酸磷酸化，但用EPO刺激未能激活Shc。EPO、IL-2和IL-15激活了衔接蛋白Shp2的酪氨酸磷酸化以及Shp2/Grb2/细胞因子受体复合物的结合。此外，EPO、IL-2和IL-15激活了Raf1和ERK2，表明Raf1/MEK/MAP激酶途径被激活。这些结果表明，多种生化途径能够在CTLL-EPO-R中传递有丝分裂信号。EPO可以通过依赖Shc或不依赖Shc的途径激活Raf1/MEK/MAP激酶途径，并且在CTLL-EPO-R中，EPO依赖的细胞生长不需要激活Shc。
