Multiple Regions of Internalin B Contribute to Its Ability to
Turn on the Ras-Mitogen-activated Protein Kinase Pathway*
Jeremy
Copp
,
Michael
Marino§,
Manidipa
Banerjee,
Partho
Ghosh¶, and
Peter
van der Geer
From the Department of Chemistry and Biochemistry, University of
California San Diego, La Jolla, California 92093-0359
Internalin B (InlB) is a protein present on the
surface of Listeria monocytogenes that mediates bacterial
entry into mammalian cells. It is thought that InlB acts by binding
directly to the hepatocyte growth factor (HGF) receptor, present on the
surface of host cells. Binding of InlB to the HGF receptor results in mitogen-activated protein (MAP) kinase and phosphoinositide 3-kinase activation, followed by changes in the organization of the actin cytoskeleton. Here we have compared signaling by HGF and InlB. Whereas
stimulation with equivalent concentrations of HGF and InlB elicits
similar activation of the HGF receptor, we observed striking
differences in downstream activation of MAP kinase. InlB leads to a
greater activation of the Ras-MAP kinase pathway than does HGF. The
leucine-rich repeat region, which was previously shown to be sufficient
for binding and activation of the HGF receptor, lacks the ability to
super-activate the Ras-MAP kinase pathway. Analysis of a series of
deletion mutants suggests that it is the B repeat region between the
leucine-rich repeat and GW domains that endows InlB with an increased
ability to turn on the Ras-MAP kinase pathway. These unexpected
observations suggest that HGF and InlB use alternative mechanisms to
turn on cellular signaling pathways.
*
This work was supported in part by a grant from the American
Heart Association (to P. G.) and National Institutes of Health Grant
R01 AI47163 (to P. G.).The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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