the proinsulin c-peptide—a multirole model模型的胰岛素原c-peptide-a多用途.pdfVIP

Experimental Diab. Res., 5:7–14, 2004 c Copyright Taylor and Francis Inc. ISSN: 1543-8600 print / 1543-8619 online DOI: 10.1080/15438600490424389 The Proinsulin C-peptide—A Multirole Model Donald F. Steiner Howard Hughes Medical Institute and Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA INTRODUCTION The C-peptide links the insulin A and B chains in proin- Intracellular cleavage of protein and polypeptide precursors sulin, providing thereby a means to promote their efficient is now recognized as a widely occurring biosynthetic mecha- folding and assembly in the endoplasmic reticulum dur- nism that can play many important roles in preparing biologi- ing insulin biosynthesis. It then facilitates the intracellular transport, sorting, and proteolytic processing of proinsulin cally important molecules for their function. Proinsulin was the into biologically active insulin in the maturing secretory first precursor protein of this type to be identified, sequenced, granules of the β cells. These manifold functions impose sig- and shown to precede insulin in appropriately designed pulse- nificant constraints on the C-peptide structure that are con- chase biosynthetic labeling experiments (Steiner et al., 1969). served in evolution. After cleavage of proinsulin, the intact In insulin biosynthesis, it fulfills the important biologic role of C-peptide is stored with insulin in the soluble phase of the facilitating the formation of the correct secondary and tertiary secretory granules and is subsequently released in equimo- lar