Nerve Growth Factor-induced Growth Arrest and Induction of p21 in NIH-3T3 Cells Expressing TrkA

• Published in: The Journal of biological chemistry Vol. 270; no. 52; pp. 30841 - 30844
• Main Author: Decker, Stuart J.
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 29.12.1995
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.52.30841

Treatment of NIH-3T3 cells expressing human TrkA with nerve growth factor (NGF) resulted in a rapid cessation of growth. Cells stopped dividing within 24 h of NGF treatment and failed to divide as long as NGF was present, accumulating in the G 1 stage of the cell cycle. NGF caused a prolonged activation of mitogen-activated protein kinase relative to EGF. NGF treatment of cells greatly increased levels of the p21 protein, an inhibitor of cyclin-dependent kinases, without affecting levels of p27 or p16 . Levels of p21 remained elevated for at least 48 h following NGF addition. EGF had little effect on p21 expression in the same parental cells expressing the human EGF receptor. NGF treatment of cells completely inhibited the activity of the cyclin-dependent protein kinases CDK2 and CDK4. Inhibition correlated with a 10-20-fold increase in the amount of p21 complexed with CDK2 and CDK4. Levels of CDK2 and CDK4 were decreased following NGF treatment of cells; however, levels of cyclin E and cyclin D were increased. These data indicate that NGF can induce cell cycle arrest of NIH-3T3, perhaps through modulation of p21 levels. The data also show that distinct signals are generated by TrkA versus the EGF receptor in NIH-3T3 cells.