title: Peptides derived from central turn motifs within integrin αIIb and αV cytoplasmic tails inhibit integrin activation.
abstract: We previously found that peptides derived from the full length of integrin αIIb and αV cytoplasmic tails inhibited their parent integrin activation, respectively. Here we showed that the cell-permeable peptides corresponding to the conserved central turn motif within αIIb and αV cytoplasmic tails, myr-KRNRPPLEED (αIIb peptide) and myr-KRVRPPQEEQ (αV peptide), similarly inhibited both αIIb and αV integrin activation. Pre-treatment with αIIb or αV peptides inhibited Mn(2+)-activated αIIbβ3 binding to soluble fibrinogen as well as the binding of αIIbβ3-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 αV ligand vitronectin. These results suggest that αIIb and αV peptides share a same mechanism in regulating integrin function. Using αIIb peptide as a model, we found that replacement of RPP with AAA significantly attenuated the inhibitory activity of αIIb peptide. Furthermore, we found that αIIb peptide specifically bound to β-tubulin in cells. Our work suggests that the central motif of α 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 αIIb and αV integrin activation.
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5.
authors.forename: Xinlei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5. Electronic address: tahaas2014@gmail.com.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Haas
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000187:drug effects* / Q000235:genetics; D006224:Cricetinae; D003412:Cricetulus; D003593:Cytoplasm / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D039421:Integrin alpha2 / Q000008:administration & dosage / Q000235:genetics*; D039564:Integrin alphaV / Q000008:administration & dosage* / Q000235:genetics; D061986:MCF-7 Cells; D010455:Peptides / Q000008:administration & dosage* / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: C056564:ITGA2B protein, human; D039421:Integrin alpha2; D039564:Integrin alphaV; D010455:Peptides; D005340:Fibrinogen
keywords: Cytoplasmic tails; Integrin activation; Integrin α(IIb) and α(V); Turn motif