Inhibition of GSK-3beta promotes survival and proliferation of megakaryocytic cells through a beta-catenin-independent pathway.

ABSTRACT: The interaction of thrombopoietin (TPO) with its receptor c-Mpl initiates intracellular signals that are critical for megakaryopoiesis. Previously we and others have shown that TPO activates PI3K and Akt and that this pathway is important for megakaryocyte growth. Here, we investigate the importance of the Akt substrate glycogen synthase kinase (GSK)-3beta in TPO signaling. GSK-3beta is phosphorylated and inhibited by Akt as part of the PI3K pathway. GSK-3beta can also be inhibited by Wnt signaling through a distinct mechanism, leading to reduced phosphorylation and accumulation of the transcription factor beta-catenin. Therefore, we asked if TPO and Wnt3a can both inhibit GSK-3beta in megakaryocytic cells, and if they can act synergistically to promote cell growth. Although both TPO and s

SUBMITTER: Soda M 

PROVIDER: S-EPMC2677808 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature