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Miscellaneous (14)

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Abstract #51096 Published in IGR 14-3

Shp-2 regulates the TrkB receptor activity in the retinal ganglion cells under glaucomatous stress

Gupta VK; You Y; Klistorner A; Graham SL
Biochimica et Biophysica Acta 2012; 1822: 1643-1649

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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.

Australian School of Advanced Medicine, Macquarie University, Australia. vivek.gupta@mq.edu.au

Full article

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Classification:

3.6 Cellular biology (Part of: 3 Laboratory methods)
11.8 Neuroprotection (Part of: 11 Medical treatment)

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