| | |  | | | | Record from Web of Science® | | | | | | |
| Regulation of cell survival by secreted proneurotrophins |
|
|
| Author(s): Lee R, Kermani P, Teng KK, Hempstead BL |
| Source: SCIENCE Volume: 294 Issue: 5548 Pages: 1945-1948 Published: NOV 30 2001 |
| Times Cited: 464 References: 24 |
| 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 p75(NTR)-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 p75(NTR) to mediate apoptosis and mature forms activating Trk receptors to promote survival. |
| Document Type: Article |
| Language: English |
| Reprint Address: Hempstead, BL (reprint author), Cornell Univ, Weill Med Coll, Dept Med, Div Hematol, 1300 York Ave, New York, NY 10021 USA |
Addresses:
1. Cornell Univ, Weill Med Coll, Dept Med, Div Hematol, New York, NY 10021 USA |
| Publisher: AMER ASSOC ADVANCEMENT SCIENCE, 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 497PQ |
| ISSN: 0036-8075 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |