Regulation of LKB1/STRAD Localization and Function by E-cadherin

Overview

Journal Curr Biol

Publisher Cell Press

Specialty Biology

Date 2008 Dec 27

PMID 19110428

Citations 43

Authors

Michael Sebbagh

Marie-Josee Santoni

Brian Hall

Jean-Paul Borg

Martin A Schwartz

Affiliations

Soon will be listed here.

Abstract

LKB1 kinase is a tumor suppressor that is causally linked to Peutz-Jeghers syndrome. In complex with the pseudokinase STRAD and the scaffolding protein MO25, LKB1 phosphorylates and activates AMPK family kinases, which mediate many cellular processes. The prototypical family member AMPK regulates cell energy metabolism and epithelial apicobasal polarity. This latter event is also dependent on E-cadherin-mediated adherens junctions (AJs) at lateral borders. Strikingly, overexpression of LKB1/STRAD can also trigger establishment of epithelial polarity in the absence of cell-cell or cell-matrix contacts. However, the upstream factors that normally govern LKB1/STRAD function are unknown. Here we show by immunostaining and fluorescence resonance energy transfer that active LKB1/STRAD kinase complex colocalizes with E-cadherin at AJs. LKB1/STRAD localization and AMPK phosphorylation require E-cadherin-dependent maturation of AJs. However, LKB1/STRAD complex kinase activity is E-cadherin independent. These data suggest that in polarized epithelial cells, E-cadherin regulates AMPK phosphorylation by controlling the localization of the LKB1 complex. The LKB1 complex therefore appears to function downstream of E-cadherin in tumor suppression.

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