The Listeria protein internalin B mimics hepatocyte growth factor-induced receptor trafficking

Ning Li, Guang Sheng Xiang, Hatem Dokainish, Keith Ireton, Lisa Elferink

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Increased hepatocyte growth factor receptor (HGFR) signaling correlates closely with neoplastic invasion and metastatic potential of many human cancers. Hepatocyte growth factor receptor signaling is initiated by binding the physiological ligand HGF or the internalin B (InlB) protein of Listeria monocytogenes. Subsequent degradation of endocytosed HGFR terminates receptor signaling. Previously reported discrepancies in InlB and HGF-induced HGFR signaling could reflect differences in receptor internalization and degradation in response to these distinct ligands. We report that soluble InlB and HGF are mechanistically equivalent in triggering clathrin-dependent endocytosis and lysosomal degradation of HGFR. After internalization, InlB and HGF colocalize with Rab5, EEA1 and the transferrin receptor in classical early endosomes. Hepatocyte growth factor receptor internalization was prevented by overexpression of dominant negative mutants of dynamin 1 and epidermal growth factor phosphorylation substrate 15, but not caveolin 1, the GTPase Arf6 or the cholesterol-chelating drug Nystatin. Thus, HGFR internalization is principally clathrin-mediated and is not regulated by clathrin-independent pathways. Phosphatidylinositol 3-kinase signaling and HGF-regulated tyrosine kinase substrate were not required for ligand-triggered internalization of HGFR but were essential for subsequent lysosomal degradation. Thus, soluble InlB and HGF induce HGFR endocytosis and degradation by indistinguishable mechanisms, suggesting that InlB may be exploited to regulate pathogenic HGFR signaling.

Original languageEnglish (US)
Pages (from-to)459-473
Number of pages15
JournalTraffic
Volume6
Issue number6
DOIs
StatePublished - Jun 2005

Fingerprint

Proto-Oncogene Proteins c-met
Listeria
Hepatocyte Growth Factor
Proteins
Clathrin
Degradation
Endocytosis
Ligands
Dynamin I
IgA receptor
Phosphatidylinositol 3-Kinase
Caveolin 1
Nystatin
Phosphorylation
Transferrin Receptors
Endosomes
GTP Phosphohydrolases
Substrates
Chelation
Epidermal Growth Factor

Keywords

  • Clathrin
  • Endocytosis
  • HGFR
  • InlB
  • Listeria

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Structural Biology
  • Molecular Biology
  • Genetics

Cite this

The Listeria protein internalin B mimics hepatocyte growth factor-induced receptor trafficking. / Li, Ning; Xiang, Guang Sheng; Dokainish, Hatem; Ireton, Keith; Elferink, Lisa.

In: Traffic, Vol. 6, No. 6, 06.2005, p. 459-473.

Research output: Contribution to journalArticle

Li, Ning ; Xiang, Guang Sheng ; Dokainish, Hatem ; Ireton, Keith ; Elferink, Lisa. / The Listeria protein internalin B mimics hepatocyte growth factor-induced receptor trafficking. In: Traffic. 2005 ; Vol. 6, No. 6. pp. 459-473.
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