Department of Medicine, University of Colorado, Anschutz Medical Campus, School of Medicine, Aurora, CO 80045, USA.
Mol Cell Endocrinol. 2013 Jul 15;374(1-2):92-100. doi: 10.1016/j.mce.2013.04.018. Epub 2013 May 3.
The membrane tyrosine kinase receptors, AXL and MET, are implicated in GnRH neuron migration and/or survival. We hypothesized that the receptors with their ligands, GAS6 and HGF, respectively may cross-talk in GnRH neuronal function. In NLT GnRH neuronal cells, MET co-immunoprecipitated with AXL, although HGF or GAS6 did not transphosphorylate AXL or MET, respectively. Co-expression of a kinase dead AXL blocked HGF activation of MET and indirectly AKT and p38MAPK. Silencing of AXL decreased HGF's ability to phosphorylate MET and activate AXL's downstream effectors, p38MAPK and AKT. HGF/MET signaling modulated neuron migration dependent and independent of AXL co-expression and p38MAPK. Conversely, AXL's control of GnRH neuronal survival was dependent on HGF/MET signaling. Together, these data support that the importance of membrane tyrosine kinase receptor crosstalk to regulate neuronal cell-specific developmental functions.
膜酪氨酸激酶受体 AXL 和 MET 参与 GnRH 神经元的迁移和/或存活。我们假设这些受体及其配体 GAS6 和 HGF 可能在 GnRH 神经元功能中相互作用。在 NLT GnRH 神经元细胞中，MET 与 AXL 共免疫沉淀，尽管 HGF 或 GAS6 分别不能使 AXL 或 MET 发生转磷酸化。共表达激酶失活的 AXL 阻断了 HGF 对 MET 的激活，以及间接的 AKT 和 p38MAPK。AXL 的沉默降低了 HGF 使 MET 磷酸化和激活 AXL 的下游效应物 p38MAPK 和 AKT 的能力。HGF/MET 信号转导调节神经元迁移，与 AXL 共表达和 p38MAPK 无关。相反，AXL 对 GnRH 神经元存活的控制依赖于 HGF/MET 信号转导。总之，这些数据支持膜酪氨酸激酶受体相互作用对于调节神经元细胞特定发育功能的重要性。
