QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 17, Issue 8, 3345-3355, August 2006

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E06-03-0193v1 17/8/3345    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Elbert, M. Articles by Müsch, A. Search for Related Content PubMed PubMed Citation Articles by Elbert, M. Articles by Müsch, A.

PAR1b Promotes Cell–Cell Adhesion and Inhibits Dishevelled-mediated Transformation of Madin-Darby Canine Kidney Cells

Maya Elbert^*,, David Cohen^*, and Anne Müsch^*

*Margaret M. Dyson Vision Research Institute and Graduate Program in Pharmacology, Cornell University Medical College, New York, NY 10021

Submitted March 13, 2006; Revised May 1, 2006; Accepted May 8, 2006
Monitoring Editor: Ben Margolis

Mammalian Par1 is a family of serine/threonine kinases comprised of four homologous isoforms that have been associated with tumor suppression and differentiation of epithelial and neuronal cells, yet little is known about their cellular functions. In polarizing kidney epithelial (Madin-Darby canine kidney [MDCK]) cells, the Par1 isoform Par1b/MARK2/EMK1 promotes the E-cadherin–dependent compaction, columnarization, and cytoskeletal organization characteristic of differentiated columnar epithelia. Here, we identify two functions of Par1b that likely contribute to its role as a tumor suppressor in epithelial cells. 1) The kinase promotes cell–cell adhesion and resistance of E-cadherin to extraction by nonionic detergents, a measure for the association of the E-cadherin cytoplasmic domain with the actin cytoskeleton, which is critical for E-cadherin function. 2) Par1b attenuates the effect of Dishevelled (Dvl) expression, an inducer of wnt signaling that causes transformation of epithelial cells. Although Dvl is a known Par1 substrate in vitro, we determined, after mapping the PAR1b-phosphorylation sites in Dvl, that PAR1b did not antagonize Dvl signaling by phosphorylating the wnt-signaling molecule. Instead, our data suggest that both proteins function antagonistically to regulate the assembly of functional E-cadherin–dependent adhesion complexes.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Anne Müsch ( amuesch{at}mail.med.cornell.edu)

This article has been cited by other articles:

				T. Sapir, S. Sapoznik, T. Levy, D. Finkelshtein, A. Shmueli, T. Timm, E.-M. Mandelkow, and O. Reiner Accurate Balance of the Polarity Kinase MARK2/Par-1 Is Required for Proper Cortical Neuronal Migration J. Neurosci., May 28, 2008; 28(22): 5710 - 5720. [Abstract] [Full Text] [PDF]

				A. F. Hezel, S. Gurumurthy, Z. Granot, A. Swisa, G. C. Chu, G. Bailey, Y. Dor, N. Bardeesy, and R. A. DePinho Pancreatic Lkb1 Deletion Leads to Acinar Polarity Defects and Cystic Neoplasms Mol. Cell. Biol., April 1, 2008; 28(7): 2414 - 2425. [Abstract] [Full Text] [PDF]

				T. Terabayashi, T. J. Itoh, H. Yamaguchi, Y. Yoshimura, Y. Funato, S. Ohno, and H. Miki Polarity-Regulating Kinase Partitioning-Defective 1/Microtubule Affinity-Regulating Kinase 2 Negatively Regulates Development of Dendrites on Hippocampal Neurons J. Neurosci., November 28, 2007; 27(48): 13098 - 13107. [Abstract] [Full Text] [PDF]

				D. Cohen, Y. Tian, and A. Musch Par1b Promotes Hepatic-type Lumen Polarity in Madin Darby Canine Kidney Cells via Myosin II- and E-Cadherin-dependent Signaling Mol. Biol. Cell, June 1, 2007; 18(6): 2203 - 2215. [Abstract] [Full Text] [PDF]

				A. H. Broquet, C. Lenoir, A. Gardet, C. Sapin, S. Chwetzoff, A.-M. Jouniaux, S. Lopez, G. Trugnan, M. Bachelet, and G. Thomas Hsp70 Negatively Controls Rotavirus Protein Bioavailability in Caco-2 Cells Infected by the Rotavirus RF Strain J. Virol., February 1, 2007; 81(3): 1297 - 1304. [Abstract] [Full Text] [PDF]