PMID: 9552163Apr 29, 1998Paper

Selective blockade of axonogenesis in cultured hippocampal neurons by the tyrosine phosphatase inhibitor orthovanadate

Journal of Neurobiology
J W Mandell, G A Banker

Abstract

Protein tyrosine phosphorylation has been implicated in several aspects of neurite outgrowth regulation. To address specific roles in early neuronal morphogenesis, hippocampal neurons in culture were treated with the tyrosine phosphatase inhibitor orthovanadate. This treatment completely suppressed axon formation, yet enhanced formation of minor neurites. The inhibition of axonogenesis was dose dependent and occurred in parallel with a marked increase in cellular phosphotyrosine immunoreactivity, which was especially concentrated within neuritic growth cones and showed partial colocalization with f-actin. Both the blockade of axonogenesis and the elevation of phosphotyrosine were completely reversible. An additional and unexpected effect of orthovanadate was the appearance of many binucleate neurons. Immunoblotting experiments using a phosphotyrosine-specific antibody revealed an orthovanadate-induced reversible hyperphosphorylation of several protein bands, especially of two at 115 and 125 kD. These data suggest a potentially important role for tyrosine phosphatases and their phosphoprotein substrates in axonogenesis.

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Citations

Jan 22, 2010·Archives of Pharmacal Research·Cheng PengDing-Kun Zhang
Feb 24, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Nina V StieglerMarcel Leist
Oct 26, 2010·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Joshua A HarrillWilliam R Mundy
Dec 31, 2002·Molecular and Cellular Neurosciences·Subhas C BiswasEduardo R Macagno
Apr 23, 1999·Journal of Neuroscience Research·M P Mattson, J Partin
Sep 2, 1999·Biochemical and Biophysical Research Communications·B S WeeksA Ahmad

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