The Signaling Adaptor Gab1 Regulates Cell Polarity by Acting as a PAR Protein Scaffold

Yang, Z., Xue, B., Umitsu, M., Ikura, M., Muthuswamy, S. K., Neel, B. G. (August 2012) The Signaling Adaptor Gab1 Regulates Cell Polarity by Acting as a PAR Protein Scaffold. Molecular Cell, 47 (3). pp. 469-483.

URL: http://www.ncbi.nlm.nih.gov/pubmed/22883624
DOI: 10.1016/j.molcel.2012.06.037

Abstract

Cell polarity plays a key role in development and is disrupted in tumors, yet the molecules and mechanisms that regulate polarity remain poorly defined. We found that the scaffolding adaptor GAB1 interacts with two polarity proteins, PAR1 and PAR3. GAB1 binds PAR1 and enhances its kinase activity. GAB1 brings PAR1 and PAR3 into a transient complex, stimulating PAR3 phosphorylation by PAR1. GAB1 and PAR6 bind the PAR3 PDZ1 domain and thereby compete for PAR3 binding. Consequently, GAB1 depletion causes PAR3 hypophosphorylation and increases PAR3/PAR6 complex formation, resulting in accelerated and enhanced tight junction formation, increased transepithelial resistance, and lateral domain shortening. Conversely, GAB1 overexpression, in a PAR1/PAR3-dependent manner, disrupts epithelial apical-basal polarity, promotes multilumen cyst formation, and enhances growth factor-induced epithelial cell scattering. Our results identify GAB1 as a negative regulator of epithelial cell polarity that functions as a scaffold for modulating PAR protein complexes on the lateral membrane. © 2012 Elsevier Inc.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell polarity
organs, tissues, organelles, cell types and functions > cell types and functions
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein characterization
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein structure rendering
CSHL Authors:
Communities: CSHL Cancer Center Shared Resources > Microscopy Service
CSHL labs > Muthuswamy lab
CSHL Cancer Center Program > Signal Transduction
Depositing User: Matt Covey
Date: 10 August 2012
Date Deposited: 17 Jan 2013 20:35
Last Modified: 16 Oct 2015 15:38
PMCID: PMC3462001
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27088

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