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Infection and Immunity, January 2009, p. 60-69, Vol. 77, No. 1
0019-9567/09/$08.00+0     doi:10.1128/IAI.00639-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Abelson Tyrosine Kinase Facilitates Salmonella enterica Serovar Typhimurium Entry into Epithelial Cells{triangledown}

Kim Thien Ly1 and James E. Casanova1,2*

Department of Microbiology,1 Department of Cell Biology, University of Virginia Health System, Charlottesville, Virginia 22908-07322

Received 23 May 2008/ Returned for modification 25 June 2008/ Accepted 10 October 2008

The intracellular gram-negative bacterial pathogen Salmonella enterica serovar Typhimurium gains entry into nonphagocytic cells by manipulating the assembly of the host actin cytoskeleton. S. enterica serovar Typhimurium entry requires a functional type III secretion system, a conduit through which bacterial effector proteins are directly translocated into the host cytosol. We and others have previously reported the enhancement of tyrosine kinase activities during Salmonella serovar Typhimurium infection; however, neither specific kinases nor their targets have been well characterized. In this study, we investigated the roles of the cellular Abelson tyrosine kinase (c-Abl) and the related protein Arg in the context of serovar Typhimurium infection. We found that bacterial internalization was inhibited by more than 70% in cells lacking both c-Abl and Arg and that treatment of wild-type cells with a pharmaceutical inhibitor of the c-Abl kinase, STI571 (imatinib), reduced serovar Typhimurium invasion efficiency to a similar extent. Bacterial infection led to enhanced phosphorylation of two previously identified c-Abl substrates, the adaptor protein CT10 regulator of kinase (CrkII) and the Abelson-interacting protein Abi1, a component of the WAVE2 complex. Furthermore, overexpression of the nonphosphorylatable form of CrkII resulted in decreased invasion. Taken together, these findings indicate that c-Abl is activated during S. enterica serovar Typhimurium infection and that its phosphorylation of multiple downstream targets is functionally important in bacterial internalization.

* Corresponding author. Mailing address: Dept. of Cell Biology, University of Virginia Health System, Box 800732, 1300 Jefferson Park Ave., Charlottesville, VA 22908-0732. Phone: (434) 243-4821. Fax: (434) 982-3912. E-mail: jec9e{at}virginia.edu

{triangledown} Published ahead of print on 20 October 2008.

Editor: B. A. McCormick

Infection and Immunity, January 2009, p. 60-69, Vol. 77, No. 1
0019-9567/09/$08.00+0     doi:10.1128/IAI.00639-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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