Downregulation of LAR tyrosine phosphatase prevents apoptosis and augments NGF-induced neurite outgrowth

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Abstract

The identity of the protein tyrosine phosphatases (PTPs) regulating cell death and responses to neurotrophins during neural development remain unknown. To determine if the leukocyte common antigen-related (LAR) PTP regulates these processes, PC12 cells were made LAR-deficient via stable transfection with an LAR antisense transgene. LAR-deficient cells demonstrated a stable novel phenotype, including a two-fold increase in nerve growth factor- but not fibroblast growth factor-induced neurite outgrowth. Upon serum-deprivation, LAR-deficient cells exhibited a two- to three-fold decrease in cell death. The findings that an endogenous PTP promotes cell death and counter-regulates neurotrophin actions introduce a major new receptor gene family to neurotrophic processes and suggest novel strategies for preventing cell death and augmenting neurotrophin function. (C) 2000 John Wiley and Sons, Inc.

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Tisi, M. A., Xie, Y., Yeo, T. T., & Longo, F. M. (2000). Downregulation of LAR tyrosine phosphatase prevents apoptosis and augments NGF-induced neurite outgrowth. Journal of Neurobiology, 42(4), 477–486. https://doi.org/10.1002/(SICI)1097-4695(200003)42:4<477::AID-NEU8>3.0.CO;2-B

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