Role of prohormone convertases in the tissue-specific processing of proglucagon.
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| Abstract |
Proglucagon (proG) is processed in a tissue-specific manner to glucagon in the pancreas and to gilcentin, oxyntomodulin, glucagon-like peptide (GLP)-1, and GLP-2 in the intestine. Recombinant vaccinia virus (vv) vectors were used to infect prohormone convertase 1 (PC1) or PC2 into nonendocrine (BHK-proG) cells, which stably express proG. Similarly, endocrine (GH3, AtT-20) cells were coinfected with proG along with PC1 or PC2 alone, or in combination with furin, PACE4, PC5a, or PC5b. Cell extracts were analyzed for various proG-derived peptides by RIA of fractions obtained from HPLC. Upon infection of BHK-proG cells with either vv: furin or vv:PC1, glicentin was produced, while vv: PC2 did not process proG. In GH3 and AtT-20 cells, vv:PC1 produced glicentin, oxyntomodulin, GLP-1(1-37), GLP-1(7-37), and GLP-2. All other enzymes tested produced only glicentin. Interestingly, no enzyme or combination produced glucagon. Coinfection of GH3 cells with vv:PC2 and members of the chromogranin family of peptides, including chromogranin A and B and secretogranin II, as well as the PC2-binding protein 7B2, did not result in processing to glucagon. It is concluded that: 1) PC1 is responsible for the processing of proG to produce the intestinal peptides glicentin, oxyntomodulin, GLP-1(1-37), GLP-1(7-37), and GLP-2, and 2) PC2 processes proG to glicentin but does not produce glucagon, alone or in combination with other enzymes or with known molecular chaperones.
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| Authors | S Dhanvantari, N G Seidah, P L Brubaker |
| Journal | Molecular endocrinology (Baltimore, Md.) (Mol Endocrinol) Vol. 10 Issue 4 Pg. 342-55 (Apr 1996) ISSN: 0888-8809 [Print] United States |
| PMID | 8721980 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
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