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Updated: Aug 13, 2026

Rapid Generation of Amyloid from Native Proteins In vitro
05:48

Rapid Generation of Amyloid from Native Proteins In vitro

Published on: December 5, 2013

Transforming growth factor-alpha and beta-amyloid precursor protein share a secretory mechanism

J Arribas1, J Massagué

  • 1Cell Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York 10021.

The Journal of Cell Biology
|February 1, 1995
PubMed

Insights

Researchers identified a common system responsible for cleaving and releasing membrane protein ectodomains. This system is crucial for processing various cell surface proteins, including transforming growth factor alpha (TGF-alpha) and beta-amyloid precursor protein (beta-APP).

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Regulated cleavage and release of membrane protein ectodomains are critical cellular processes affecting numerous cell surface proteins.
  • The precise mechanisms governing this ectodomain shedding remain largely uncharacterized, with questions about shared versus independent pathways.

Purpose of the Study:

  • To investigate whether cell surface proteins are cleaved via a common mechanism or multiple independent pathways.
  • To identify the components involved in the regulated cleavage of membrane protein ectodomains.

Main Methods:

  • Mutagenesis of Chinese hamster ovary (CHO) cells to select clones with defects in membrane protein ectodomain cleavage.
  • Treatment of wild-type and mutant CHO cells with the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA).
  • Analysis of cleavage defects in transforming growth factor alpha (TGF-alpha), beta-amyloid precursor protein (beta-APP), and other PMA-stimulated cell surface proteins.

Main Results:

  • Mutant CHO clones were identified that were unable to cleave TGF-alpha, even upon PMA stimulation.
  • These mutant clones also exhibited a loss of ability to cleave structurally unrelated membrane proteins, including beta-APP and other PMA-inducible cell surface proteins.
  • The observed defects were independent of protein expression, cell surface transport, or turnover, and affected both PKC-dependent and PKC-independent cleavage mechanisms.

Conclusions:

  • A common system mediates the regulated cleavage and secretion of membrane protein ectodomains.
  • This system's components respond to multiple activators and act on diverse protein substrates.
  • The findings suggest a unified mechanism for ectodomain shedding, impacting various cell signaling pathways.

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