Met receptor tyrosine kinase degradation is altered in response to the leucine-rich repeat of the Listeria invasion protein internalin B

Xiu Gao, Marta Lorinczi, Kristen S. Hill, Natasha C. Brooks, Hatem Dokainish, Keith Ireton, Lisa Elferink

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Entry of the bacterial pathogen Listeria monocytogenes into host epithelial cells is critical for infection and virulence. One major pathway for Listeria entry involves binding of the bacterial protein Internalin B to the host receptor tyrosine kinase Met (hepatocyte growth factor receptor). Activation of Met and downstream signaling cascades is critical for Listeria entry. Internalin B is composed of several structural domains including an N-terminal leucine-rich repeat that is sufficient for binding Met and stimulating downstream signal transduction. Internalin B is monomeric, whereas the leucine-rich repeat is dimeric when expressed as an isolated fragment. The different quaternary states of Internalin B and the leucine-rich repeat suggest that these two Met ligands might cause distinct biological effects. Here we demonstrate that Internalin B and the leucine-rich repeat fragment exhibit agonist properties that differentially influence Met down-regulation in lysosomes. Specifically, Met stability is increased in response to the leucine-rich repeat fragment compared with Internalin B. Interestingly, Internalin B and the leucine-rich repeat stimulate equivalent rates of clathrin-mediated Met internalization. However, the leucine-rich repeat is defective in promoting lysosomal down-regulation of Met and instead enhances receptor recycling to the cell surface. In addition, the leucine-rich repeat causes prolonged Met activation (phosphorylation) and increased cell motility compared with Interna-lin B. Taken together, our findings indicate that individual domains of Internalin B differentially regulate Met trafficking. The ability of the leucine-rich repeat fragment to promote Met recycling could account for the increased cell motility induced by this ligand

Original languageEnglish (US)
Pages (from-to)774-783
Number of pages10
JournalJournal of Biological Chemistry
Volume284
Issue number2
DOIs
StatePublished - Jan 9 2009

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Listeria
Receptor Protein-Tyrosine Kinases
Leucine
Degradation
Proteins
Cell Movement
Recycling
Down-Regulation
Chemical activation
Proto-Oncogene Proteins c-met
Ligands
IgA receptor
Signal transduction
Clathrin
Phosphorylation
Bacterial Proteins
Listeria monocytogenes
Pathogens
Lysosomes
Virulence

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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Met receptor tyrosine kinase degradation is altered in response to the leucine-rich repeat of the Listeria invasion protein internalin B. / Gao, Xiu; Lorinczi, Marta; Hill, Kristen S.; Brooks, Natasha C.; Dokainish, Hatem; Ireton, Keith; Elferink, Lisa.

In: Journal of Biological Chemistry, Vol. 284, No. 2, 09.01.2009, p. 774-783.

Research output: Contribution to journalArticle

Gao, Xiu ; Lorinczi, Marta ; Hill, Kristen S. ; Brooks, Natasha C. ; Dokainish, Hatem ; Ireton, Keith ; Elferink, Lisa. / Met receptor tyrosine kinase degradation is altered in response to the leucine-rich repeat of the Listeria invasion protein internalin B. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 2. pp. 774-783.
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