Multiple signals activate cleavage of the membrane transforming growth factor-alpha precursor.

Cleavage of the membrane-anchored precursor for transforming growth factor-alpha (TGF-alpha), a rate-limiting step in the generation of soluble TGF-alpha, can be stimulated by phorbol esters acting via protein kinase C. In the present study, activators of other intracellular signaling pathways were tested for their ability to stimulate pro-TGF-alpha cleavage in Chinese hamster ovary cells transfected with a pro-TGF-alpha cDNA. Treatment with the Ca2+ ionophore, A23187, rapidly increased the rate of pro-TGF-alpha cleavage over 25-fold. This effect of A23187 on pro-TGF-alpha cleavage was dependent on the influx of extracellular calcium and was largely independent of protein kinase C activation. In contrast, phorbol 12-myristate 13-acetate stimulation of pro-TGF-alpha cleavage via activation of protein kinase C did not require extracellular calcium. Stimulation of pro-TGF-alpha cleavage by serum was largely independent of both protein kinase C and extracellular calcium influx, whereas activators of protein kinase A and protein kinase G did not stimulate pro-TGF-alpha cleavage. These results suggest that regulation of pro-TGF-alpha cleavage is a complex process that can be controlled by extracellular agents via at least three distinct signal transduction pathways.

• Publication year

  1991

• Venue

  Journal of Biological Chemistry

• Publication date

  1991-03-25

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1016/s0021-9258(19)67662-3PMID 2005114
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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