HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gross, D. J. Articles by Halban, P. A. Search for Related Content PubMed PubMed Citation Articles by Gross, D. J. Articles by Halban, P. A. Social Bookmarking                      What's this?

J. Biol. Chem., Vol. 264, Issue 36, 21486-21490, Dec, 1989

Deletion of a highly conserved tetrapeptide sequence of the proinsulin connecting peptide (C-peptide) inhibits proinsulin to insulin conversion by transfected pituitary corticotroph (AtT20) cells

DJ Gross, L Villa-Komaroff, CR Kahn, GC Weir and PA Halban
Elliot P. Joslin Research Laboratory, Joslin Diabetes Center, Boston, Massachusetts.

The biological function of the connecting peptide (C-peptide) of proinsulin is unknown. Comparison of all known C-peptide sequences reveals the presence of a highly conserved peptide sequence, Glu/Asp-X- Glu/Asp (X being a hydrophobic amino acid), adjacent to the Arg-Arg doublet at the B chain/C-peptide junction. Furthermore, the next amino acid in the C-peptide sequence is also acidic in many animal species. To test the possible involvement of this hydrophilic domain in insulin biosynthesis, we constructed a mutant of the rat proinsulin II gene lacking the first four amino acids of the C-peptide and expressed either the normal (INS) on the mutated (INSDEL) genes in the AtT20 pituitary corticotroph cell line. In both cases immunoreactive insulin (IRI) was stored by the cells and released upon stimulation by cAMP. In the INS expressing cells, the majority of IRI, whether stored or released in response to a secretagogue, was mature insulin. By contrast, most of the stored and releasable IRI in the INSDEL expressing cells appeared to be (mutant) proinsulin or conversion intermediate with little detectable native insulin. Release of the mutant proinsulin and/or conversion intermediates was stimulated by cAMP. These results suggest that the mutant proinsulin was appropriately targeted to secretory granules and released predominantly via the regulated pathway, but that the C-peptide deletion prevented its conversion to native insulin.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R. Kuliawat, D. Prabakaran, and P. Arvan Proinsulin Endoproteolysis Confers Enhanced Targeting of Processed Insulin to the Regulated Secretory Pathway Mol. Biol. Cell, June 1, 2000; 11(6): 1959 - 1972. [Abstract] [Full Text]

				C. B. Verchere, M. Paoletta, M. Neerman-Arbez, K. Rose, J.-C. Irminger, R. L. Gingerich, S. E. Kahn, and P. A. Halban Des-(, , , , )C-Peptide. A NOVEL SECRETORY PRODUCT OF THE RAT PANCREATIC BETA CELL PRODUCED BY TRUNCATION OF PROINSULIN CONNECTING PEPTIDE IN SECRETORY GRANULES J. Biol. Chem., November 1, 1996; 271(44): 27475 - 27481. [Abstract] [Full Text] [PDF]