OVEREXPRESSION OF THE TRK TYROSINE KINASE RAPIDLY ACCELERATES NERVE GROWTH FACTOR-INDUCED DIFFERENTIATION

被引:313
作者
HEMPSTEAD, BL
RABIN, SJ
KAPLAN, L
REID, S
PARADA, LF
KAPLAN, DR
机构
[1] NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD 21701 USA
[2] NCI, FREDERICK CANC RES & DEV CTR, MMCL, EUKARYOT SIGNAL TRANSDUCT GRP, FREDERICK, MD 21701 USA
[3] NCI, FREDERICK CANC RES & DEV CTR, MGL, MOLEC EMBRYOL SECT, FREDERICK, MD 21701 USA
关键词
D O I
10.1016/0896-6273(92)90241-5
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
To investigate the role of the gp140trk receptor tyrosine kinase in nerve growth factor (NGF)-induced differentiation, we have overexpressed gp140trk in the NGF-responsive PC12 cell line. Here we demonstrate that overexpression of gp140trk results in marked changes in NGF-induced differentiation. Whereas PC12 cells elaborated neurites after 2 days of continuous exposure to NGF, PC12 cells overexpressing gp140trk by 20-fold (trk-PC12) began this process within hours. Compared with wild-type PC12 cells, trk-PC12 exhibited an increase in both high and low affinity NGF-binding sites. Furthermore, trk-PC12 cells displayed an enhanced level of NGF-dependent gp140trk autophosphorylation, and this activity was sustained for many hours following ligand binding. The tyrosine phosphorylation or activity of several cellular proteins, such as PLC-gamma1, PI-3 kinase, and Erk1 and the expression of the mRNA for the late response gene transin were also sustained as a consequence of gp140trk overexpression. The data indicate that overexpression of gp140trk in PC12 cells markedly accelerates NGF-induced differentiation pathways, possibly through the elevation of gp140trk tyrosine kinase activity.
引用
收藏
页码:883 / 896
页数:14
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