Peptides derived from central turn motifs within integrin alpha(IIb) and alpha(V) cytoplasmic tails inhibit integrin activation

摘要

We previously found that peptides derived from the full length of integrin alpha(IIb) and alpha(V) cytoplasmic tails inhibited their parent integrin activation, respectively. Here we showed that the cell-permeable peptides corresponding to the conserved central turn motif within alpha(IIb) and alpha(V) cytoplasmic tails, myr-KRNRPPLEED (am peptide) and myr-KRVRPPQEE Q(alpha(v) peptide), similarly inhibited both Mb and civ integrin activation. Pre-treatment with alpha(IIb) or alpha(V) peptides inhibited Mn2+-activated alpha(IIb)beta(3) binding to soluble fibrinogen as well as the binding of alpha(IIb)beta(3)-expressing Chinese Hamster Ovary cells to immobilized fibrinogen. Our turn peptides also inhibited adhesion of two breast cancer cell lines (MDA-MB-435 and MCF7) to civ ligand vitronectin. These results suggest that (In and civ peptides share a same mechanism in regulating integrin function. Using alpha(IIb) peptide as a model, we found that replacement of RPP with AAA significantly attenuated the inhibitory activity of Mb peptide. Furthermore, we found that lam peptide specifically bound to beta-tubulin in cells. Our work suggests that the central motif of ce. tails is an anchoring point for cytoskeletons during integrin activation and integrin-mediated cell adhesion, and its function depends on the turn structure at RPP. However, post-treatment of peptides derived from the full-length tail or from the turn motif did not reverse alpha(IIb) and alpha(V) integrin activation. (C) 2014 Elsevier Inc. All rights reserved.