HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Berger, S. A. Articles by Ziltener, H. J. Search for Related Content PubMed PubMed Citation Articles by Berger, S. A. Articles by Ziltener, H. J. Social Bookmarking                      What's this?

Volume 271, Number 38, Issue of September 20, 1996 pp. 23431-23437
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Identification of a Bacterial Inhibitor of Protein Kinases
MECHANISM AND ROLE IN HOST CELL INVASION

(Received for publication, March 14, 1996, and in revised form, June 18, 1996)

Stuart A. Berger ^§ , Kevin Rowan , Hamish D. Morrison and Hermann J. Ziltener ^''

From the  Wellesley Hospital Research Institute, Toronto, Ontario, Canada M4Y 1J3, the ^§ Department of Immunology, University of Toronto, Toronto, Ontario, Canada M5S 1X8, the  Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia V6T 123, and the ^'' Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 123

We show that Escherichia coli produce a factor that inhibits the activity of tyrosine and serine/threonine protein kinases. The factor is a protein found in the periplasmic compartment and is also secreted into the culture medium. Using a particle concentration fluorescence immunoassay specific for tyrosine kinase activity and inhibition of the tyrosine kinase p56^lck, we purified this factor to apparent homogeneity. Analysis of trypsin-digested fragments by mass spectrometry identified the inhibitor as the bacterial periplasmic protein UDP-sugar hydrolase, an enzyme with potent and nonspecific 5-nucleotidase activity. Overexpression of the enzyme in bacteria leads to coordinate increases in both 5-nucleotidase and p56^lck inhibitory activity, confirming the identity of the inhibitor. The kinase inhibitory activity appears to be due to the formation of adenosine, which we show is inhibitory for p56^lck, cAMP-dependent protein kinase, and casein kinase. Overexpression of UDP-sugar hydrolase leads to an increase in the recovery of enteropathogenic E. coli following infection of HeLa cell monolayers and corresponding alterations in tyrosine-phosphorylated host proteins. These results suggest that UDP-sugar hydrolase may be an important factor affecting host cell function following intracellular bacterial infection.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. Zhang, D. M. Conrad, J. J. Butler, C. Zhao, J. Blay, and D. W. Hoskin Adenosine Acts through A2 Receptors to Inhibit IL-2-Induced Tyrosine Phosphorylation of STAT5 in T Lymphocytes: Role of Cyclic Adenosine 3',5'-Monophosphate and Phosphatases J. Immunol., July 15, 2004; 173(2): 932 - 944. [Abstract] [Full Text] [PDF]

				D. Innes, I. R. Beacham, C.-A. Beven, M. Douglas, M. W. Laird, J. C. Joly, and D. M. Burns The cryptic ushA gene (ushAc) in natural isolates of Salmonella enterica (serotype Typhimurium) has been inactivated by a single missense mutation Microbiology, July 1, 2001; 147(7): 1887 - 1896. [Abstract] [Full Text] [PDF]

				E.-N. N'Diaye, X. Darzacq, C. Astarie-Dequeker, M. Daffe, J. Calafat, and I. Maridonneau-Parini Fusion of Azurophil Granules with Phagosomes and Activation of the Tyrosine Kinase Hck Are Specifically Inhibited During Phagocytosis of Mycobacteria by Human Neutrophils J. Immunol., November 1, 1998; 161(9): 4983 - 4991. [Abstract] [Full Text] [PDF]