title: GW domains of the Listeria monocytogenes invasion protein InlB are required for potentiation of Met activation.
abstract: The Listeria monocytogenes protein InlB promotes intracellular invasion by activating the receptor tyrosine kinase Met. Earlier studies have indicated that the LRR fragment of InlB is sufficient for Met activation, but we show that this is not the case unless the LRR fragment is artificially dimerized through a disulphide bond. In contrast, activation of Met proceeds through monomers of intact InlB and, at physiologically relevant concentrations, requires coordinated action in cis of both InlB N-terminal LRR region and C-terminal GW domains. The GW domains are shown to be crucial for potentiating Met activation and inducing intracellular invasion, with these effects depending on association between GW domains and glycosaminoglycans. Glycosaminoglycans do not alter the monomeric state of InlB, and are likely to enhance Met activation through a receptor-mediated mode, as opposed to the ligand-mediated mode observed for the LRR fragment. Surprisingly, we find that gC1q-R, a host protein implicated in InlB-mediated invasion, specifically antagonizes rather than enhances InlB signalling, and that interaction between InlB and gC1q-R is unnecessary for bacterial invasion. Lastly, we demonstrate that HGF, the endogenous ligand of Met, substitutes for InlB in promoting intracellular invasion, suggesting that no special properties are required of InlB in invasion besides its hormone-like mimicry of HGF.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0314, USA.
authors.forename: Manidipa
authors.initials: M
authors.lastname: Banerjee
authors.forename: Jeremy
authors.initials: J
authors.lastname: Copp
authors.forename: Danka
authors.initials: D
authors.lastname: Vuga
authors.forename: Michael
authors.initials: M
authors.lastname: Marino
authors.forename: Tara
authors.initials: T
authors.lastname: Chapman
authors.forename: Peter
authors.initials: P
authors.lastname: van der Geer
authors.forename: Partho
authors.initials: P
authors.lastname: Ghosh
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D016466:CHO Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D019281:Dimerization; D006025:Glycosaminoglycans / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D008089:Listeria monocytogenes / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D008958:Models, Molecular; D009154:Mutation; D017434:Protein Structure, Tertiary; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D011951:Receptors, Complement / Q000502:physiology; D017384:Sequence Deletion / Q000235:genetics / Q000502:physiology; D014709:Vero Cells
chemical_list: D001426:Bacterial Proteins; D006025:Glycosaminoglycans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011951:Receptors, Complement; C032402:complement 1q receptor; C095768:inlB protein, Listeria monocytogenes; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met