title: Dephosphorylation of beta-arrestin 1 in glioblastomas.
abstract: Beta-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 beta-arrestin 1 phosphorylation and activation status could play a role in gliomagenesis. Using monoclonal anti-phospho-(serine 412)- and total beta-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 beta-arrestin 1 phosphorylation in nonneoplastic brain tissue, particularly in neurons and neuropil. Most Grade II and III gliomas retained high beta-arrestin 1 phosphorylation. By contrast, most of the glioblastoma samples (58/81) showed nearly complete beta-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 beta-arrestin 1 phosphorylation without altering total beta-arrestin 1 levels. These results suggest that beta-arrestin 1 dephosphorylation/inactivation is associated with aspects of the malignant behavior of glioblastomas.
authors.affiliation: Department of Pathology, University of Virginia Health System, Charlottesville, VA 22903, USA. jwm2m@virginia.edu
authors.forename: James W
authors.initials: JW
authors.lastname: Mandell
authors.forename: George
authors.initials: G
authors.lastname: Glass
authors.forename: Erwin P
authors.initials: EP
authors.lastname: Gianchandani
authors.forename: Corinne N
authors.initials: CN
authors.lastname: Locke
authors.forename: Samson
authors.initials: S
authors.lastname: Amos
authors.forename: Thomas David
authors.initials: TD
authors.lastname: Bourne
authors.forename: David
authors.initials: D
authors.lastname: Schiff
authors.forename: Jason A
authors.initials: JA
authors.lastname: Papin
mesh_terms: D019390:Arrestins / Q000378:metabolism*; D045744:Cell Line, Tumor; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D012189:Retrospective Studies; D012694:Serine / Q000378:metabolism; D014162:Transfection; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins
chemical_list: C000605253:ARRB1 protein, human; D019390:Arrestins; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D012694:Serine; D048052:Mitogen-Activated Protein Kinase 3