期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
卷 1822, 期 11, 页码 1643-1649出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2012.07.016
关键词
Retinal ganglion cell; Glaucoma; Optic nerve; TrkB receptor; Shp2 phosphatase; Immunoprecipitation
资金
- Ophthalmic Research Institute of Australia (ORIA)
- MQNS grant
- Allergan Australia
Tropomyosin-receptor-kinase B (TrkB receptor) activation plays an important role in the survival of retinal ganglion cells (RGCs). This study reports a novel finding that, SH2 domain-containing phosphatase-2 (Shp-2) binds to the TrkB receptor in RGCs and negatively regulates its activity under glaucomatous stress. This enhanced binding of TrkB and Shp2 is mediated through caveolin. Caveolin 1 and 3 undergo hyper-phosphorylation in RGCs under stress and bind to the Shp2 phosphatase. Shp2 undergoes activation under glaucomatous stress conditions in RGCs in vivo with a concurrent loss of TrkB activity. Inhibiting the Shp2 phosphatase restored TrkB activity in cells exposed to excitotoxic and oxidative stress. Collectively, these findings implicate a molecular basis of Shp2 mediated TrkB deactivation leading to RGC degeneration observed in glaucoma. (C) 2012 Elsevier B.V. All rights reserved.
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