Literature search services are currently unavailable. During our hosting provider's UPS upgrade we experienced a hardware failure and are currently working to resolve the issue.

Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

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

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 PKCdelta binds in vivo and in vitro to the cytoplasmic domain of MDC9/meltrin-gamma/ADAM9, a member of the metalloprotease-disintegrin family. Furthermore, the presence of constitutively active PKCdelta or MDC9 results in the shedding of the ectodomain of proHB-EGF, whereas MDC9 mutants lacking the metalloprotease domain, as well as kinase-negative PKCdelta, suppress the TPA-induced shedding of the ectodomain. These results suggest that MDC9 and PKCdelta are involved in the stimulus-coupled shedding of the proHB-EGF ectodomain.

Pubmed ID: 9857183


  • Izumi Y
  • Hirata M
  • Hasuwa H
  • Iwamoto R
  • Umata T
  • Miyado K
  • Tamai Y
  • Kurisaki T
  • Sehara-Fujisawa A
  • Ohno S
  • Mekada E


The EMBO journal

Publication Data

December 15, 1998

Associated Grants


Mesh Terms

  • ADAM Proteins
  • Catalytic Domain
  • Disintegrins
  • Epidermal Growth Factor
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Isoenzymes
  • Membrane Proteins
  • Metalloendopeptidases
  • Muscle Proteins
  • Mutation
  • Protein Binding
  • Protein Kinase C
  • Protein Kinase C-delta
  • Protein Precursors
  • Protein Processing, Post-Translational
  • Recombinant Proteins
  • Solubility
  • Tetradecanoylphorbol Acetate