Multiple signals activate cleavage of the membrane transforming growth factor-α precursor Journal Article
| Authors: | Pandiella, A.; Massagué, J. |
| Article Title: | Multiple signals activate cleavage of the membrane transforming growth factor-α precursor |
| Abstract: | Cleavage of the membrane-anchored precursor for transforming growth factor-α (TGF-α), a rate-limiting step in the generation of soluble TGF-α, 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-α cleavage in Chinese hamster ovary cells transfected with a pro-TGF-α cDNA. Treatment with the Ca2+ ionophore, A23187, rapidly increased the rate of pro-TGF-α cleavage over 25-fold. This effect of A23187 on pro-TGF-α 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-α cleavage via activation of protein kinase C did not require extracellular calcium. Stimulation of pro-TGF-α 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-α cleavage. These results suggest that regulation of pro-TGF-α cleavage is a complex process that can be controlled by extracellular agents via at least three distinct signal transduction pathways. |
| Keywords: | signal transduction; nonhuman; animal cell; animal; cell line; calcium; enzyme activation; animalia; protein processing; kinetics; protein kinase c; transforming growth factor alpha; electrophoresis, polyacrylamide gel; tetradecanoylphorbol acetate; cho cell; cricetinae; cricetulus; cricetulus griseus; protein precursor; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, non-p.h.s.; hamsters; calcimycin |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 266 |
| Issue: | 9 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 1991-03-25 |
| Start Page: | 5769 |
| End Page: | 5773 |
| Language: | English |
| PUBMED: | 2005114 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 27 September 2019 -- Source: Scopus |
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