Systematic analysis of bacterial effector-postsynaptic density 95/disc large/zonula occludens-1 (PDZ) domain interactions demonstrates Shigella OspE protein promotes protein kinase C activation via PDLIM proteins.

Autor:	Yi CR; From the Division of Infectious Diseases, Massachusetts General Hospital, Cambridge, Massachusetts 02139., Allen JE; the Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, and., Russo B; From the Division of Infectious Diseases, Massachusetts General Hospital, Cambridge, Massachusetts 02139, Departments of Microbiology and Immunobiology and., Lee SY; the Program in Immunology and., Heindl JE; Departments of Microbiology and Immunobiology and., Baxt LA; From the Division of Infectious Diseases, Massachusetts General Hospital, Cambridge, Massachusetts 02139., Herrera BB; From the Division of Infectious Diseases, Massachusetts General Hospital, Cambridge, Massachusetts 02139., Kahoud E; From the Division of Infectious Diseases, Massachusetts General Hospital, Cambridge, Massachusetts 02139., MacBeath G; Systems Biology, Harvard Medical School, Boston, Massachusetts 02115., Goldberg MB; From the Division of Infectious Diseases, Massachusetts General Hospital, Cambridge, Massachusetts 02139, Departments of Microbiology and Immunobiology and marcia.goldberg@mgh.harvard.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2014 Oct 24; Vol. 289 (43), pp. 30101-13. Date of Electronic Publication: 2014 Sep 08.
DOI:	10.1074/jbc.M114.595868
Abstrakt:	Diseases caused by many Gram-negative bacterial pathogens depend on the activities of bacterial effector proteins that are delivered into eukaryotic cells via specialized secretion systems. Effector protein function largely depends on specific subcellular targeting and specific interactions with cellular ligands. PDZ domains are common domains that serve to provide specificity in protein-protein interactions in eukaryotic systems. We show that putative PDZ-binding motifs are significantly enriched among effector proteins delivered into mammalian cells by certain bacterial pathogens. We use PDZ domain microarrays to identify candidate interaction partners of the Shigella flexneri effector proteins OspE1 and OspE2, which contain putative PDZ-binding motifs. We demonstrate in vitro and in cells that OspE proteins interact with PDLIM7, a member of the PDLIM family of proteins, which contain a PDZ domain and one or more LIM domains, protein interaction domains that participate in a wide variety of functions, including activation of isoforms of protein kinase C (PKC). We demonstrate that activation of PKC during S. flexneri infection is attenuated in the absence of PDLIM7 or OspE proteins and that the OspE PDZ-binding motif is required for wild-type levels of PKC activation. These results are consistent with a model in which binding of OspE to PDLIM7 during infection regulates the activity of PKC isoforms that bind to the PDLIM7 LIM domain. (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)
Databáze:	MEDLINE
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