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

✍ Scribed by Tisi, Michelle A. ;Xie, Youmei ;Yeo, Tracy T. ;Longo, Frank M.

• Book ID: 101261073
• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 174 KB
• Volume: 42
• Category: Article
• ISSN: 0022-3034
• DOI: 10.1002/(sici)1097-4695(200003)42:4<477::aid-neu8>3.0.co;2-b

✦ Synopsis

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.