RIFLE: a novel ring zinc finger-leucine-rich repeat containing protein, regulates select cell adhesion molecules in PC12 cells.
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-3alpha/beta (GSK-3alpha/beta) resulting in the inhibition of GSK-3 kinase activity and increase of beta-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.
Li
Baolin
B
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
Su
Yuan
Y
Ryder
John
J
Yan
Lei
L
Na
Songqing
S
Ni
Binhui
B
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015820:Cadherins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D024141:Collagen Type IV / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D000090263:Leucine-Rich Repeat Proteins; D008969:Molecular Sequence Data; D016716:PC12 Cells; D010766:Phosphorylation; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology; D014018:Tissue Distribution; D015534:Trans-Activators / Q000378:metabolism*; D051153:Wnt Proteins; D016335:Zinc Fingers; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D015815:Cell Adhesion Molecules; D024141:Collagen Type IV; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D005353:Fibronectins; D000090263:Leucine-Rich Repeat Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; C488631:RIFLE protein, rat; D015534:Trans-Activators; D051153:Wnt Proteins; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha; D002118:Calcium