title: Shp-2 regulates the TrkB receptor activity in the retinal ganglion cells under glaucomatous stress.
abstract: 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.
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Australia. vivek.gupta@mq.edu.au
authors.forename: Vivek K
authors.initials: VK
authors.lastname: Gupta
authors.forename: Yuyi
authors.initials: Y
authors.lastname: You
authors.forename: Alexander
authors.initials: A
authors.lastname: Klistorner
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Graham
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism; D051244:Caveolin 3 / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D005901:Glaucoma / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense; D020221:Optic Nerve Injuries; D018384:Oxidative Stress; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D018909:src Homology Domains
chemical_list: C495549:Cav3 protein, rat; D051242:Caveolin 1; D051244:Caveolin 3; D020319:Oligodeoxyribonucleotides, Antisense; D020813:Receptor, trkB; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11