Patapoutian A, Reichardt L F
Department of Cell Biology, The Scripps Research Institute and Genomics Institute, Novartis Research Foundation, La Jolla, CA 92037, USA.
Curr Opin Neurobiol. 2001 Jun;11(3):272-80. doi: 10.1016/s0959-4388(00)00208-7.
The four mammalian neurotrophins - NGF, BDNF, NT-3 and NT-4 - each bind and activate one or more of the Trk family of receptor tyrosine kinases. Through these receptors, neurotrophins activate many intracellular signaling pathways, including those controlled by Ras, the Cdc42/Rac/RhoG protein family, MAPK, PI3K and PLC-gamma, thereby affecting both development and function of the nervous system. During the past two years, several novel signaling pathways controlled by Trk receptors have been characterized, and it has become clear that membrane transport and sorting controls Trk-receptor-mediated signaling because key intermediates are localized to different membrane compartments. Three-dimensional structures of the Trk receptors, in one instance in association with a neurotrophin, have revealed the structural bases underlying specificity in neurotrophin signaling.
四种哺乳动物神经营养因子——神经生长因子（NGF）、脑源性神经营养因子（BDNF）、神经营养因子-3（NT-3）和神经营养因子-4（NT-4）——各自结合并激活一个或多个酪氨酸激酶受体Trk家族成员。通过这些受体，神经营养因子激活许多细胞内信号通路，包括由Ras、Cdc42/Rac/RhoG蛋白家族、丝裂原活化蛋白激酶（MAPK）、磷脂酰肌醇-3激酶（PI3K）和磷脂酶C-γ（PLC-γ）控制的信号通路，从而影响神经系统的发育和功能。在过去两年中，已经鉴定出几种由Trk受体控制的新型信号通路，并且很明显膜转运和分选控制Trk受体介导的信号传导，因为关键中间体定位于不同的膜区室。Trk受体的三维结构，其中一种情况是与神经营养因子结合，揭示了神经营养因子信号传导特异性的结构基础。
