Autocrine regulation of membrane transforming growth factor-α cleavage Journal Article
| Authors: | Baselga, J.; Mendelsohn, J.; Kim, Y. M.; Pandiella, A. |
| Article Title: | Autocrine regulation of membrane transforming growth factor-α cleavage |
| Abstract: | Transforming growth factor α (TGF-α) is biosynthesized as a membrane- bound precursor protein, proTGF-α, that undergoes sequential endoproteolytic cleavages to release a soluble form of the factor. In the present study, we have analyzed the biosynthesis and regulation of TGF-α production in human tumor-derived cell lines that endogenously express pro-TGF-α and the epidermal growth factor (EGF) receptor. These cells biosynthesized membrane- anchored forms of the TGF-α that accumulated on the cell surface. Membrane- bound pro-TGF-α interacted with the EGF receptor, and complexes of receptor and pro-TGF-α contained tyrosine-phosphorylated receptor. Activation of the EGF receptor by soluble EGF or TGF-α had a dual effect on TGF-α production: an increase in pro-TGF-α mRNA levels and an increase in pro-TGF-α cleavage. These effects were largely prevented by preincubation with an anti-EGF receptor monoclonal antibody that blocked ligand binding. Growth factor autoinduction of cleavage could be stimulated by several second messenger pathways that are activated by the EGF receptor, including protein kinase C and intracellular calcium, and by other alternative mechanisms. EGF- stimulated cleavage of pro-TGF-α could be partially blocked by inhibition of these second messenger pathways. These results suggest that juxtacrine stimulation takes place in human tumor cells that coexpress both the EGF receptor and membrane-anchored TGF-α and that TGF-α is able to induce its own endoproteolytic cleavage by activating the EGF receptor. |
| Keywords: | human cell; carcinoma, squamous cell; nonhuman; animal cell; animals; gene expression; protein degradation; epidermal growth factor receptor; receptor, epidermal growth factor; enzyme activation; tumor cell culture; tumor cells, cultured; transfection; monoclonal antibody; gene expression regulation, neoplastic; biosynthesis; protein processing, post-translational; messenger rna; recombinant proteins; cell membrane; down regulation; rats; antibodies; calcium cell level; autoradiography; cysteine; transforming growth factor alpha; phorbol 13 acetate 12 myristate; tetradecanoylphorbol acetate; cho cell; cho cells; cricetinae; protein precursors; second messenger; humans; human; male; female; priority journal; article; sulfur radioisotopes; calcimycin |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 271 |
| Issue: | 6 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 1996-02-09 |
| Start Page: | 3279 |
| End Page: | 3284 |
| Language: | English |
| DOI: | 10.1074/jbc.271.6.3279 |
| PUBMED: | 8621731 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
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