Ma. Tisi et al., Downregulation of LAR tyrosine phosphatase prevents apoptosis and augmentsNGF-induced neurite outgrowth, J NEUROBIOL, 42(4), 2000, pp. 477-486
The identity of the protein tyrosine phosphatases (PTPs) regulating cell de
ath 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-depriva
tion, LAR-deficient cells exhibited a two- to three-fold decrease in cell d
eath, The findings that an endogenous PTP promotes cell death and counter-r
egulates neurotrophin actions introduce a major new receptor gene family to
neurotrophic processes and suggest novel strategies for preventing cell de
ath and augmenting neurotrophin function. (C) 2000 John Wiley & Sons, Inc.*