RIFLE: A novel ring zinc finger‐leucine‐rich repeat containing protein, regulates select cell adhesion molecules in PC12 cells

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Abstract
Cell adhesion molecules play a critical role in cell contacts, whether cell–cell or cell–matrix, and are regulated by multiple signaling pathways. In this report, we identify a novel ring zinc finger‐leucine‐rich repeat containing protein (RIFLE) and show that RIFLE, expressed in PC12 cells, enhances the Serine (Ser)21/9 phosphorylation of glycogen synthase kinase‐3α/β (GSK‐3α/β) resulting in the inhibition of GSK‐3 kinase activity and increase of β‐catenin levels. RIFLE expression also is associated with elevated E‐cadherin protein levels but not N‐cadherin. The regulation of these cell adhesion‐associated molecules by RIFLE is accompanied by a significant increase in cell–cell and cell–matrix adhesion. Moreover, increase in cell–cell adhesion but not cell–matrix adhesion by RIFLE can be mimicked by selective inhibition of GSK‐3. Our results suggest that RIFLE represents a novel signaling protein that mediates components of the Wnt/wingless signaling pathway and cell adhesion in PC12 cells.