Department of Nutrition, Dietetics, and Hospitality Management, Auburn University, Auburn, Alabama 36849,USA.
J Biol Chem. 2013 Aug 16;288(33):23807-13. doi: 10.1074/jbc.M112.436279. Epub 2013 Jun 7.
TrkA is a cell surface transmembrane receptor tyrosine kinase for nerve growth factor (NGF). TrkA has an NPXY motif and kinase regulatory loop similar to insulin receptor (INSR) suggesting that NGF→TrkA signaling might overlap with insulin→INSR signaling. During insulin or NGF stimulation TrkA, insulin receptor substrate-1 (IRS-1), INSR (and presumably other proteins) forms a complex in PC12 cells. In PC12 cells, tyrosine phosphorylation of INSR and IRS-1 is dependent upon the functional TrkA kinase domain. Moreover, expression of TrkA kinase-inactive mutant blocked the activation of Akt and Erk5 in response to insulin or NGF. Based on these data, we propose that TrkA participates in insulin signaling pathway in PC12 cells.
TrkA 是神经生长因子 (NGF) 的细胞表面跨膜受体酪氨酸激酶。TrkA 具有与胰岛素受体 (INSR) 相似的 NPXY 基序和激酶调节环，这表明 NGF→TrkA 信号可能与胰岛素→INSR 信号重叠。在胰岛素或 NGF 刺激下，TrkA、胰岛素受体底物-1 (IRS-1)、INSR（推测还有其他蛋白）在 PC12 细胞中形成复合物。在 PC12 细胞中，胰岛素受体和 IRS-1 的酪氨酸磷酸化依赖于功能性 TrkA 激酶结构域。此外，表达 TrkA 激酶失活突变体可阻断胰岛素或 NGF 对 Akt 和 Erk5 的激活。基于这些数据，我们提出 TrkA 参与 PC12 细胞中的胰岛素信号通路。
