Expression, localization, and activity of glycogen synthase kinase 3beta during mouse skin tumorigenesis.
Glycogen synthase kinase 3 (GSK-3) is a protein kinase that plays essential roles in the control of several developmental, metabolic, and apoptotic processes. Owing to its negative actions on several oncogenic insults, it has been considered a putative functional tumor suppressor. We studied the expression, activity, and localization of GSK-3beta during the process of chemically induced two-stage mouse skin carcinogenesis and also in the tumors generated upon subcutaneous injection of Akt-transformed keratinocytes. We found that GSK-3 activity was downregulated at the later stages of promotion by tyrosine 216 dephosphorylation and serine 9 phosphorylation. The data obtained with Akt-transformed keratinocytes clearly suggested the involvement of Akt in serine 9 phosphorylation of GSK-3beta. Finally, besides functional inactivation, significant basal activity of GSK-3beta was detected in all cases, indicating that this enzyme provides essential functions to malignant keratinocytes.
Leis
Hugo
H
Project on Cell and Molecular Biology, Centro de Investigaciones Energéticas Medioambientales y Technológicas (CIEMAT), Madrid, Spain.
Segrelles
Carmen
C
Ruiz
Sergio
S
Santos
Mirentxu
M
Paramio
Jesús M
JM
D000818:Animals; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D051379:Mice; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology
D012694:Serine; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3