The Novel Protein-tyrosine Phosphatase PTP20 Is a Positive Regulator of PC12 Cell Neuronal Differentiation

Yumiko Yamaguchi-Aoki,Axel Ullrich,Naohito Aoki

doi:10.1074/jbc.271.46.29422

Yumiko Yamaguchi-Aoki, Axel Ullrich + Show 1 more

Open Access

https://doi.org/10.1074/jbc.271.46.29422

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Abstract

A novel cytoplasmic protein-tyrosine phosphatase (PTPase) designated PTP20 was isolated from a PC12 cDNA library and shown to positively regulate the differentiation process in PC12 cells. The PTP20 open reading frame of 453 amino acids contains a single tyrosine phosphatase catalytic domain and displays closest homology to members of the PTP-PEST protein-tyrosine phosphatase family. Transient expression of PTP20 in Rat-1 cells resulted in the expression of a 50-kDa protein which exhibited PTPase activity in vitro. Expression of the 2.3-kilobase PTP20 mRNA increased during differentiation of nerve growth factor (NGF)-stimulated PC12 cells. Consistent with this observation, stable overexpression of PTP20 in PC12 cells resulted in accelerated neurite formation following NGF treatment. These findings suggest a positive regulatory role of PTP20 in NGF-dependent neuronal differentiation of PC12 cells.

Highlights

A novel cytoplasmic protein-tyrosine phosphatase when nerve growth factor (NGF) binds to the extracellular domain of its cognate (PTPase) designated PTP20 was isolated from a PC12 receptor
Expression of tyrosine phosphatase inhibitor orthovanadate can inhibit the the 2.3-kilobase PTP20 mRNA increased during differentiation of nerve growth factor (NGF)-stimulated PC12 cells
Consistent with this observation, stable overexpression of PTP20 in PC12 cells resulted in accelerated neurite formation following NGF treatment

Summary

Introduction

A novel cytoplasmic protein-tyrosine phosphatase when NGF binds to the extracellular domain of its cognate (PTPase) designated PTP20 was isolated from a PC12 receptor. Expression of tyrosine phosphatase inhibitor orthovanadate can inhibit the the 2.3-kilobase PTP20 mRNA increased during differentiation of nerve growth factor (NGF)-stimulated PC12 cells. We show the molecular cloning of a novel PTPase, named PTP20, and demonstrate that this PTPase might play a positive regulatory role in NGF-induced differentiation of PC12 cells.

Results

Conclusion