Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Cell Biol. 2003 Nov 10;163(3):489-502. Epub 2003 Nov 3.

Proteolytic release of the carboxy-terminal fragment of proHB-EGF causes nuclear export of PLZF.

Author information

  • 1Department of Medical Biochemistry, Ehime University School of Medicine, Onsen-gun, Ehime 791-0295, Japan.

Abstract

Cleavage of membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) via metalloprotease activation yields amino- and carboxy-terminal regions (HB-EGF and HB-EGF-C, respectively), with HB-EGF widely recognized as a key element of epidermal growth factor receptor transactivation in G protein-coupled receptor signaling. Here, we show a biological role of HB-EGF-C in cells. Subsequent to proteolytic cleavage of proHB-EGF, HB-EGF-C translocated from the plasma membrane into the nucleus. This translocation triggered nuclear export of the transcriptional repressor, promyelocytic leukemia zinc finger (PLZF), which we identify as an HB-EGF-C binding protein. Suppression of cyclin A and delayed entry of S-phase in cells expressing PLZF were reversed by the production of HB-EGF-C. These results indicate that released HB-EGF-C functions as an intracellular signal and coordinates cell cycle progression with HB-EGF.

PMID:
14597771
[PubMed - indexed for MEDLINE]
PMCID:
PMC2173632
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk