|
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 p56lck,
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 p56lck 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 p56lck, 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]
|
 |
|
Copyright © 1996 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|