Cleavage of the membrane precursor for transforming growth factor α is a regulated process Journal Article
| Authors: | Pandiella, A.; Massagué, J. |
| Article Title: | Cleavage of the membrane precursor for transforming growth factor α is a regulated process |
| Abstract: | Transforming growth factor-alpha (TGF-alpha) is generated by cleavage of a membrane-anchored precursor protein, proTGF-alpha. ProTGF-alpha is cleaved at a slow rate and accumulates on the cell surface, thereby mediating cell-cell adhesion and mitogenic stimulation. We show here that cleavage of membrane proTGF-alpha by an elastase-like enzyme constitutes an important regulatory step in the generation of soluble TGF-alpha. Cleavage is activated in response to serum factors and tumor-promoting phorbol esters, leading to depletion of cell surface proTGF-alpha, which disperses as soluble factor. Activation of proTGF-alpha cleavage is mediated by protein kinase C-dependent and -independent mechanisms. The results demonstrate the existence of mechanisms that control the switch of TGF-alpha from a juxtacrine to a paracrine growth factor. |
| Keywords: | phorbol esters; phorbol ester; expression; factor-alpha; cells; induction; messenger-rna; factor receptors; egf receptor; tgf-alpha; growth factors; protein kinase-c; membrane proteases; prohormones |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 88 |
| Issue: | 5 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 1991-03-01 |
| Start Page: | 1726 |
| End Page: | 1730 |
| Language: | English |
| ACCESSION: | WOS:A1991FA14000028 |
| DOI: | 10.1073/pnas.88.5.1726 |
| PROVIDER: | wos |
| PMCID: | PMC51097 |
| PUBMED: | 2000380 |
| Notes: | Source: Wos |
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