A metalloprotease-disintegrin, MDC9/meltrin-γ/ADAM9 and PKCδ are involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor

Yasushi Izumi, Michinari Hirata, Hidetoshi Hasuwa, Ryo Iwamoto, Toshiyuki Umata, Kenji Miyado, Yoko Tamai, Tomohiro Kurisaki, Atsuko Sehara-Fujisawa, Shigeo Ohno, Eisuke Mekada

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456 Citations (Scopus)

Abstract

The ectodomains of many proteins located at the cell surface are shed upon cell stimulation. One such protein is the heparin-binding EGF-like growth factor (HB-EGF) that exists in a membrane-anchored form which is converted to a soluble form upon cell stimulation with TPA, an activator of protein kinase C (PKC). We show that PKCδ binds in vivo and in vitro to the cytoplasmic domain of MDC9/meltrin-γ/ADAM9, a member of the metalloprotease-disintegrin family. Furthermore, the presence of constitutively active PKCδ or MDC9 results in the shedding of the ectodomain of proHB-EGF, whereas MDC9 mutants lacking the metalloprotease domain, as well as kinase-negative PKCδ, suppress the TPA-induced shedding of the ectodomain. These results suggest that MDC9 and PKCδ are involved in the stimulus-coupled shedding of the proHB-EGF ectodomain.

Original languageEnglish
Pages (from-to)7260-7272
Number of pages13
JournalEMBO Journal
Volume17
Issue number24
DOIs
Publication statusPublished - 1998 Dec 15

Keywords

  • Ectodomain shedding
  • Heparin-binding EGF-like growth factor
  • MDC9
  • Metalloprotease-disintegrin
  • Protein kinase C

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Izumi, Y., Hirata, M., Hasuwa, H., Iwamoto, R., Umata, T., Miyado, K., Tamai, Y., Kurisaki, T., Sehara-Fujisawa, A., Ohno, S., & Mekada, E. (1998). A metalloprotease-disintegrin, MDC9/meltrin-γ/ADAM9 and PKCδ are involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor. EMBO Journal, 17(24), 7260-7272. https://doi.org/10.1093/emboj/17.24.7260