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  • Title: Met receptor tyrosine kinase degradation is altered in response to the leucine-rich repeat of the Listeria invasion protein internalin B.
    Author: Gao X, Lorinczi M, Hill KS, Brooks NC, Dokainish H, Ireton K, Elferink LA.
    Journal: J Biol Chem; 2009 Jan 09; 284(2):774-83. PubMed ID: 18990695.
    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 Internalin 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.
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