Enhancement or induction of neurite formation by a protein tyrosine phosphatase inhibitor, 3,4-dephostatin, in growth factor-treated PC12h cells.

Abstract

We studied the effect of the 3,4-dihydroxy analogue of dephostatin (3,4-dephostatin), an inhibitor of protein-tyrosine phosphatase (PTPase), on the differentiation of rat pheochromocytoma PC12 cells. 3,4-Dephostatin accelerated NGF-induced neurite formation in PC12h cells, a subline of PC12 cells, whereas the inhibitor alone did not induce neurite formation. It sustained the NGF-induced tyrosine phosphorylation of several proteins, most prominently that of mitogen-activated protein (MAP) kinase. EGF alone did not induce differentiation in PC12h cells, but it induced neurite formation in the presence of 3,4-dephostatin. The inhibitor also prolonged EGF-induced tyrosine phosphorylation and activation of MAP kinase. An inactive analogue of dephostatin, 2'-O-methyl-dephostatin showed no effect on either neurite formation or MAP kinase tyrosine phosphorylation in NGF or EGF-treated PC12h cells. Thus, we demonstrated that the PTPase inhibitor could enhance growth factor-induced differentiation in PC12 cells possibly by sustaining the MAP kinase activity.

• Authors: S Fujiwara, T Watanabe, T Nagatsu, J Gohda, M Imoto, K Umezawa
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 238 Issue 1 Pg. 213-7 (Sep 08 1997) ISSN: 0006-291X [Print] United States
• PMID: 9299481 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hydroquinones
• Nerve Growth Factors
• dephostatin
• Phosphotyrosine
• Epidermal Growth Factor
• Calcium-Calmodulin-Dependent Protein Kinases
• Protein Tyrosine Phosphatases

Topics

• Animals
• Calcium-Calmodulin-Dependent Protein Kinases (drug effects, metabolism)
• Cell Differentiation (drug effects)
• Drug Stability
• Epidermal Growth Factor (pharmacology)
• Hydroquinones (pharmacology)
• Nerve Growth Factors (pharmacology)
• Neurites (drug effects)
• PC12 Cells
• Phosphorylation (drug effects)
• Phosphotyrosine (metabolism)
• Protein Tyrosine Phosphatases (antagonists & inhibitors)
• Rats