Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Erk associates with and primes GSK-3beta for its inactivation resulting in upregulation of beta-catenin.

Molecular cell | Jul 22, 2005

http://www.ncbi.nlm.nih.gov/pubmed/16039586

Beta-catenin is upregulated in many human cancers and considered to be an oncogene. Hepatocellular carcinoma (HCC) is one of the most prevalent human malignancies, and individuals who are chronic hepatitis B virus (HBV) carriers have a greater than 100-fold increased relative risk of developing HCC. Here we report a mechanism by which HBV-X protein (HBX) upregulates beta-catenin. Erk, which is activated by HBX, associates with GSK-3beta through a docking motif ((291)FKFP) of GSK-3beta and phosphorylates GSK-3beta at the (43)Thr residue, which primes GSK-3beta for its subsequent phosphorylation at Ser9 by p90RSK, resulting in inactivation of GSK-3beta and upregulation of beta-catenin. This pathway is a general signal, as it was also observed in cell lines in which Erk-primed inactivation of GSK-3beta was regulated by IGF-1, TGF-beta, and receptor tyrosine kinase HER2, and is further supported by immunohistochemical staining in different human tumors, including cancers of the liver, breast, kidney, and stomach.

Pubmed ID: 16039586 RIS Download

Mesh terms: Amino Acid Motifs | Breast Neoplasms | Carcinoma, Hepatocellular | Cytoskeletal Proteins | Enzyme Activation | Extracellular Signal-Regulated MAP Kinases | Female | Genes, erbB-2 | Glycogen Synthase Kinase 3 | Humans | Insulin-Like Growth Factor I | Liver Neoplasms | Phosphorylation | Trans-Activators | Tumor Cells, Cultured | Up-Regulation | beta Catenin

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: CA 16672
  • Agency: NCI NIH HHS, Id: P01 CA099031
  • Agency: NCI NIH HHS, Id: R01 CA109311
  • Agency: NCI NIH HHS, Id: R01 CA58880

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.