Regulation of cell survival by secreted proneurotrophins Academic Article uri icon

Overview

MeSH Major

  • Cell Survival
  • Nerve Growth Factors
  • Protein Precursors

abstract

  • Neurotrophins are growth factors that promote cell survival, differentiation, and cell death. They are synthesized as proforms that can be cleaved intracellularly to release mature, secreted ligands. Although proneurotrophins have been considered inactive precursors, we show here that the proforms of nerve growth factor (NGF) and the proforms of brain derived neurotrophic factor (BDNF) are secreted and cleaved extracellularly by the serine protease plasmin and by selective matrix metalloproteinases (MMPs). ProNGF is a high-affinity ligand for p75(NTR) with high affinity and induced p75NTR-dependent apoptosis in cultured neurons with minimal activation of TrkA-mediated differentiation or survival. The biological action of neurotrophins is thus regulated by proteolytic cleavage, with proforms preferentially activating p75NTR to mediate apoptosis and mature forms activating Trk receptors to promote survival.

publication date

  • November 30, 2001

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1126/science.1065057

PubMed ID

  • 11729324

Additional Document Info

start page

  • 1945

end page

  • 8

volume

  • 294

number

  • 5548