Cell Growth & Differentiation, Vol 3, Issue 6 363-367, Copyright © 1992 by American Association of Cancer Research

ARTICLES

Protein tyrosine phosphatase activation during nerve growth factor-induced neuronal differentiation of PC12 cells

LF Aparicio, I Ocrant, JM Boylan and PA Gruppuso
Division of Pediatric Endocrinology and Metabolism, Rhode Island Hospital, Providence 02903.

We have studied the role of protein tyrosine phosphatases (PTPases) during neuronal differentiation of PC12 cells. Nerve growth factor (NGF), a well-characterized differentiating agent for these cells, led to a decrease in DNA synthesis within 24 h. This was accompanied by a 2- to 3-fold increase in the activity of PTPases, measured as the dephosphorylation of polyacidic or polybasic substrates phosphorylated on tyrosine. PTPase activation was independent of cell density and proportional to NGF concentration, with a half-maximal effect occurring at 0.35 nM. High-performance liquid chromatography size exclusion chromatography revealed that PTPases with molecular masses of 550, 300, and 60 kilodaltons were activated in response to NGF. Additional studies showed that the presence of NGF made PC12 cells refractory to the mitogenic effect of epidermal growth factor. Our data indicate that NGF-induced neuronal differentiation and growth arrest in PC12 cells are associated with activation of several PTPases. We speculate that PTPase activation in response to NGF may inhibit the mitogenic actions of other growth factors.

This article has been cited by other articles:

				G. Freiss, C. Puech, and F. Vignon Extinction of Insulin-Like Growth Factor-I Mitogenic Signaling by Antiestrogen-Stimulated Fas-Associated Protein Tyrosine Phosphatase-1 in Human Breast Cancer Cells Mol. Endocrinol., April 1, 1998; 12(4): 568 - 579. [Abstract] [Full Text]

				M.-F. Lin, T.-C. Meng, P. S. Rao, C. Chang, A. H. Schonthal, and F.-F. Lin Expression of Human Prostatic Acid Phosphatase Correlates with Androgen-stimulated Cell Proliferation in Prostate Cancer Cell Lines J. Biol. Chem., March 6, 1998; 273(10): 5939 - 5947. [Abstract] [Full Text] [PDF]

				M.-C. Wang, J. H. Liu, and F.-F. Wang Protein Tyrosine Phosphatase-Dependent Activation of beta -Globin and delta -Aminolevulinic Acid Synthase Genes in the Camptothecin-Induced IW32 Erythroleukemia Cell Differentiation Mol. Pharmacol., April 1, 1997; 51(4): 558 - 566. [Abstract] [Full Text]