Multiple regions of internalin B contribute to its ability to turn on the Ras-mitogen-activated protein kinase pathway.
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.
Copp
Jeremy
J
Department of Chemistry and Biochemistry, University of California San Diego, La Jolla 92093-0359, USA.
Marino
Michael
M
Banerjee
Manidipa
M
Ghosh
Partho
P
van der Geer
Peter
P
D000818:Animals; D001426:Bacterial Proteins; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D004789:Enzyme Activation; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D008089:Listeria monocytogenes / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D014443:Tyrosine / Q000378:metabolism; D014709:Vero Cells; D018631:ras Proteins / Q000378:metabolism*
D001426:Bacterial Proteins; D008565:Membrane Proteins; C095768:inlB protein, Listeria monocytogenes; D014443:Tyrosine; D017228:Hepatocyte Growth Factor; D018631:ras Proteins