Pharmaceutical Sciences Faculty Publications
Dephosphorylation of β-Arrestin 1 in Glioblastomas
Document Type
Article
Publication Date
5-2009
Journal Title
Journal of Neuropathology & Experimental Neurology
Volume
68
Issue
5
First Page
535
Last Page
541
DOI
10.1097/NEN.0b013e3181a2b8F4-9
Abstract
β-Arrestins act as signal terminators for G protein-coupled receptors; they have also been implicated as scaffolding proteins for Src and mitogen-activated protein kinase signaling pathways and transactivators of receptor tyrosine kinases, suggesting their possible role in development and oncogenic signaling. Dephosphorylation of serine 412 is necessary for Src and mitogen-activated protein kinase transactivation. We hypothesized that altered β-arrestin 1 phosphorylation and activation status could play a role in gliomagenesis. Using monoclonal anti-phospho-(serine 412)- and total β-arrestin 1 antibodies, we performed immunohistochemistry on 126 human glioma samples and 7 nonneoplastic controls and Western blot analysis on 5 glioblastomas and 5 nonneoplastic controls. We found high constitutive β-arrestin 1 phosphorylation in nonneoplastic brain tissue, particularly in neurons and neuropil. Most Grade II and III gliomas retained high β-arrestin 1 phosphorylation. By contrast, most of the glioblastoma samples (58/81) showed nearly complete β-arrestin 1 dephosphorylation by immunohistochemistry and decreased relative phosphorylation by Western blot. Expression of constitutively activated epidermal growth factor receptor vIII in U251 cells caused decreased β-arrestin 1 phosphorylation without altering total β-arrestin 1 levels. These results suggest that β-arrestin 1 dephosphorylation/inactivation is associated with aspects of the malignant behavior of glioblastomas.
Keywords
β-Arrestin, glioblastoma
Recommended Citation
Mandell, James W.; Glass, George; Gianchandani, Erwin P.; Locke, Corinne N.; Amos, Samson; Bourne, Thomas David; Schiff, David; and Papin, Jason A., "Dephosphorylation of β-Arrestin 1 in Glioblastomas" (2009). Pharmaceutical Sciences Faculty Publications. 103.
https://digitalcommons.cedarville.edu/pharmaceutical_sciences_publications/103