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Molecular and Cellular Biology, October 2005, p. 8834-8843, Vol. 25, No. 20
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.20.8834-8843.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Abl Kinases Regulate Actin Comet Tail Elongation via an N-WASP-Dependent Pathway

Elizabeth A. Burton,1 Timothy N. Oliver,2 and Ann Marie Pendergast1*

Department of Pharmacology and Cancer Biology,1 Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 277102

Received 11 March 2005/ Returned for modification 29 April 2005/ Accepted 29 July 2005

Microbial pathogens have evolved diverse strategies to modulate the host cell cytoskeleton to achieve a productive infection and have proven instrumental for unraveling the molecular machinery that regulates actin polymerization. Here we uncover a mechanism for Shigella flexneri-induced actin comet tail elongation that links Abl family kinases to N-WASP-dependent actin polymerization. We show that the Abl kinases are required for Shigella actin comet tail formation, maximal intracellular motility, and cell-to-cell spread. Abl phosphorylates N-WASP, a host cell protein required for actin comet tail formation, and mutation of the Abl phosphorylation sites on N-WASP impairs comet tail elongation. Furthermore, we show that defective comet tail formation in cells lacking Abl kinases is rescued by activated forms of N-WASP. These data demonstrate for the first time that the Abl kinases play a role in the intracellular motility and intercellular dissemination of Shigella and uncover a new role for Abl kinases in the regulation of pathogen motility.

* Corresponding author. Mailing address: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710. Phone: (919) 681-8086. Fax: (919) 681-7148. E-mail: pende014{at}mc.duke.edu.

Molecular and Cellular Biology, October 2005, p. 8834-8843, Vol. 25, No. 20
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.20.8834-8843.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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