PME-1 Protects Extracellular Signal-Regulated Kinase Pathway Activity from Protein Phosphatase 2A-Mediated Inactivation in Human Malignant Glioma.

Puustinen P, Junttila MR, Vanhatupa S, Sablina AA, Hector ME, Teittinen K, Raheem O, Ketola K, Lin S, Kast J, Haapasalo H, Hahn WC, Westermarck J
Associated Labs:
Sablina Lab (Katholieke Universiteit Leuven)
Cancer Res. 2009 Mar 17. ():.
PMID: 19293187
Extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase pathway activity is regulated by the antagonist function of activating kinases and inactivating protein phosphatases. Sustained ERK pathway activity is commonly observed in human malignancies; however, the mechanisms by which the pathway is protected from phosphatase-mediated inactivation in the tumor tissue remain obscure. Here, we show that methylesterase PME-1-mediated inhibition of the protein phosphatase 2A promotes basal ERK pathway activity and is required for efficient growth factor response. Mechanistically, PME-1 is shown to support ERK pathway signaling upstream of Raf, but downstream of growth factor receptors and protein kinase C. In malignant gliomas, PME-1 expression levels correlate with both ERK activity and cell proliferation in vivo. Moreover, PME-1 expression significantly correlates with disease progression in human astrocytic gliomas (n = 222). Together, these observations identify PME-1 expression as one mechanism by which ERK pathway activity is maintained in cancer cells and suggest an important functional role for PME-1 in the disease progression of human astrocytic gliomas. [Cancer Res 2009;69(7):OF1-8].

Want to be recognized as an author of this publication?

Create your LabLife profile and tag yourself! You will also be able to tag other authors after you log into your account.

Create New Account


What is LabLife?

LabLife is a collection of tools to help scientists organize, share and discover.

Learn more