Leon Gonzalo, Sanchez-Ruiloba Lucia, Perez-Rodriguez Andrea, Gragera Teresa, Martinez Natalia, Hernandez Silvia, Anta Berta, Calero Olga, Garcia-Dominguez Carlota A, Dura Lara M, Peña-Jimenez Daniel, Castro Judit, Zarich Natasha, Sanchez-Gomez Pilar, Calero Miguel, Iglesias Teresa, Oliva Jose L, Rojas Jose M
Unidad de Biología Celular, Unidad Funcional de Investigación de Enfermedades Crónicas, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain.
Instituto de Investigaciones Biomédicas "Alberto Sols," Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, 28029 Madrid, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain.
PLoS One. 2014 Dec 16;9(12):e114837. doi: 10.1371/journal.pone.0114837. eCollection 2014.
The Shoc2 protein has been implicated in the positive regulation of the Ras-ERK pathway by increasing the functional binding interaction between Ras and Raf, leading to increased ERK activity. Here we found that Shoc2 overexpression induced sustained ERK phosphorylation, notably in the case of EGF stimulation, and Shoc2 knockdown inhibited ERK activation. We demonstrate that ectopic overexpression of human Shoc2 in PC12 cells significantly promotes neurite extension in the presence of EGF, a stimulus that induces proliferation rather than differentiation in these cells. Finally, Shoc2 depletion reduces both NGF-induced neurite outgrowth and ERK activation in PC12 cells. Our data indicate that Shoc2 is essential to modulate the Ras-ERK signaling outcome in cell differentiation processes involved in neurite outgrowth.
Shoc2蛋白通过增强Ras与Raf之间的功能性结合相互作用，参与Ras-ERK途径的正向调节，从而导致ERK活性增加。在此，我们发现Shoc2过表达可诱导ERK持续磷酸化，尤其是在EGF刺激的情况下，而Shoc2基因敲低则抑制ERK激活。我们证明，在存在EGF的情况下，PC12细胞中异位过表达人Shoc2可显著促进神经突生长，EGF在这些细胞中诱导增殖而非分化。最后，Shoc2缺失减少了PC12细胞中NGF诱导的神经突生长和ERK激活。我们的数据表明，Shoc2对于调节参与神经突生长的细胞分化过程中的Ras-ERK信号转导结果至关重要。
