Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Dec;8(12):1854-1872.
doi: 10.1111/j.1600-0854.2007.00651.x. Epub 2007 Oct 17.

Keratinocyte growth factor receptor ligands target the receptor to different intracellular pathways

Francesca Belleudi  1 , Laura Leone  1 , Valerio Nobili  1 , Salvatore Raffa  1   2 , Federica Francescangeli  1 , Maddalena Maggio  1 , Stefania Morrone  1 , Cinzia Marchese  1 , Maria Rosaria Torrisi  1   2
Affiliations
Free article

Keratinocyte growth factor receptor ligands target the receptor to different intracellular pathways

Francesca Belleudi et al. Traffic. 2007 Dec.
Free article

Abstract

The keratinocyte growth factor receptor (KGFR)/fibroblast growth factor receptor 2b is activated by high-affinity-specific interaction with two different ligands, keratinocyte growth factor (KGF)/fibroblast growth factor (FGF)7 and FGF10/KGF2, which are characterized by an opposite requirement of heparan sulfate proteoglycans and heparin for binding to the receptor. We investigated here the possible different endocytic trafficking of KGFR, induced by the two ligands. Immunofluorescence and immunoelectron microscopy analysis showed that KGFR internalization triggered by either KGF or FGF10 occurs through clathrin-coated pits. Immunofluorescence confocal microscopy using endocytic markers as well as tumor susceptibility gene 101 (TSG101) silencing demonstrated that KGF drives KGFR to the degradative pathway, while FGF10 targets the receptor to the recycling endosomes. Biochemical analysis showed that KGFR is ubiquitinated and degraded after KGF treatment but not after FGF10 treatment, and that the alternative fate of KGFR might depend on the different ability of the receptor to phosphorylate the fibroblast growth factor receptor substrate 2 (FRS2) substrate and to recruit the ubiquitin ligase c-Cbl. The recycling endocytic pathway followed by KGFR upon FGF10 stimulation correlates with the higher mitogenic activity exerted by this ligand on epithelial cells compared with KGF, suggesting that the two ligands may play different functional roles through the regulation of the receptor endocytic transport.

PubMed Disclaimer

References

    1. Grose R, Dickson C. Fibroblast growth factor signaling in tumorigenesis. Cytokine Growth Factor Rev 2005;16:179-186.
    1. Szebebenyi G, Fallon JF. Fibroblast growth factor as multi-functional signaling factors. Int Rev Cytol 1999;185:45-106.
    1. Dailey L, Ambrosetti D, Mansukhani A, Basilico C. Mechanisms underlying differential responses to FGF signaling. Int Rev Cytol 1999;16:233-247.
    1. Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev 2005;16:139-149.
    1. Cheon HG, LaRochelle WJ, Bottaro DP, Burgess WH, Aaronson SA. High affinity binding sites for related fibroblast growth factor ligands reside within different receptor immunoglobulin-like domains. Proc Natl Acad Sci U S A 1994;91:989-993.

Publication types

Substances

LinkOut - more resources