TY - JOUR
T1 - Overexpression of the trk tyrosine kinase rapidly accelerates nerve growth factor-induced differentiation
AU - Hempstead, Barbara L.
AU - Rabin, Stuart J.
AU - Kaplan, Leni
AU - Reid, Susan
AU - Parada, Luis F.
AU - Kaplant, David R.
N1 - Funding Information:
The authors thank M. Chao, L. Greene, and D. Morrison for thoughtful discussion; M. Chao, J. Salzet, and M. Vetter for ctiti-cal reading of the manuscript; J. Blenis, S. G. Rhee, and D. Mot-tison for antibodies; T. Cuttan, J. Milbtandt, A. Levi, C. Ciment, and E. Ziff for cDNAs; K. Nikolics and G. Button for recombinant NCF; and J. Blenis for communicating results prior to publication. We also thank R. Fredrickson and L. van Houten for photog taphy and R. Handley for assistance with the manuscript. This work was supported in part by grants from the National Cancer Institute, the American Cancer Society, the American Health Assistance Foundation, and the Match of Dimes (to 8. L. H.) and by the National Cancer Institute, DHHS, under contract no. NOI-CO-74101 with ABL (S. L. R., S. R., L. F. P., and D. R. K).
PY - 1992/11
Y1 - 1992/11
N2 - To investigate the role of the gp140trk receptor tyrosine kinase in nerve growth factor (NGF)-induced differentiation, we have overexpressed gpl40trk 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 overexpressiog 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-γ1, 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.
AB - To investigate the role of the gp140trk receptor tyrosine kinase in nerve growth factor (NGF)-induced differentiation, we have overexpressed gpl40trk 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 overexpressiog 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-γ1, 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.
UR - http://www.scopus.com/inward/record.url?scp=0026468503&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026468503&partnerID=8YFLogxK
U2 - 10.1016/0896-6273(92)90241-5
DO - 10.1016/0896-6273(92)90241-5
M3 - Article
C2 - 1384575
AN - SCOPUS:0026468503
SN - 0896-6273
VL - 9
SP - 883
EP - 896
JO - Neuron
JF - Neuron
IS - 5
ER -