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Integrin Ligands (integrin + ligand)
Selected AbstractsSynthesis and Biological Evaluation of New Conformationally Biased Integrin Ligands Based on a Tetrahydroazoninone Scaffold [cf. (VII)].CHEMINFORM, Issue 29 2007Luca Banfi Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] A pseudosymmetric cell adhesion regulatory domain in the ,7 tail of the integrin ,4,7 that interacts with focal adhesion kinase and srcEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2006Geoffrey Abstract The ,7 integrins ,4,7 and ,E,7 play key roles in forming the gut-associated lymphoid tissue, and contribute to chronic inflammation. The ,4,7 integrin-mediated adhesion of activated lymphocytes is largely due to a transient increase in avidity from ligand-induced clustering of ,4,7 at the cell-surface. Here, we report that L and D enantiomers of a cell-permeable peptide YDRREY encompassing residues 735,740 of the cytoplasmic tail of the ,7 subunit inhibit the adhesion of T cells to ,7 integrin ligands. The YDRREY peptide abrogated mucosal addressin cell adhesion molecule-1-induced clustering of ,4,7 on the surface of activated T cells. A mutated form of the YDRREY peptide carrying either single or double conservative mutations at Tyr735Phe and Tyr740Phe was unable to inhibit T cell adhesion, suggesting that both tandem tyrosines are critical for activity. The YDRREY peptide was bound and phosphorylated by focal adhesion kinase and src, which may serve to sequester cytoskeletal proteins to the cytoplasmic domain of ,4,7. The quasi-palindromic sequence YDRREY within the ,7 cytoplasmic tail constitutes a cell adhesion regulatory domain that modulates the interaction of ,7-expressing leukocytes with their endothelial and epithelial ligands. Cell-permeable peptidomimetics based on this motif have utility as anti-inflammatory reagents for the treatment of chronic inflammatory disease. [source] Modulation of integrin antagonist signaling by ligand binding of the heparin-binding domain of vitronectin to the ,V,3 integrinJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2008Laura A. Maile Abstract The interaction between the arginine glycine and aspartic acid motif (RGD) of integrin ligands such as vitronectin and the integrin receptor ,V,3 in mediating cell attachment has been well described. Similarly, the ability of disintegrins, small RGD containing peptides, to inhibit cell attachment and other cellular processes has also been studied extensively. Recently, we characterized a second site of interaction between vitronectin and its integrin partner. We determined that amino acids within the heparin-binding domain of vitronectin bind to a cysteine loop (C-loop) region of ,3 and that this interaction is required for the positive effects of ,V,3 ligand occupancy on IGF-I signaling in smooth muscle cells. In this study we examine the signaling events activated following ligand binding of disintegrins to the ,V,3 and the ability of these signals to be regulated by binding of the heparin-binding domain of vitronectin. We demonstrate that disintegrin ligand binding activates a series of events including the sequential activation of the tyrosine kinases c-Src and Syk. This leads to the activation of calpain and the cleavage of the ,3 cytoplasmic tail. Addition of vitronectin or a peptide homologous to the heparin-binding domain inhibited activation of this pathway. Our results suggest that the signaling events that occur following ligand binding to the ,V,3 integrin reflects a balance between the effects mediated through the RGD binding site interaction and the effects mediated by the heparin binding site interaction and that for intact vitronectin the effect of the heparin-binding domain predominates. J. Cell. Biochem. 105: 437,446, 2008. © 2008 Wiley-Liss, Inc. [source] Cross-talk between the insulin-like growth factor (IGF) axis and membrane integrins to regulate cell physiologyJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2010James Beattie The biology of cross-talk between activated growth factor receptors and cell-surface integrins is an area which has attracted much interest in recent years (Schwartz and Ginsberg, 2002). This review discusses the relationship between the insulin-like growth factor (IGF) axis and cell-surface integrin receptors in the regulation of various aspects of cell physiology. Key to these interactions are signals transmitted between integrins and the IGF-I receptor (IGF-IR) when either or both are bound to their cognate ligands and we will review the current state of knowledge in this area. The IGF axis comprises many molecular components and we will also discuss the potential role of these species in cross-talk with the integrin receptor. With respect to integrin ligands, we will mainly focus on the well-characterized interactions of the two extracellular matrix (ECM) glycoproteins fibronectin (FN) and vitronectin (VN) with cell-surface ligands, and, how this affects activity through the IGF axis. However, we will also highlight the importance of other integrin activation mechanisms and their impact on IGF activity. J. Cell. Physiol. 224: 605,611, 2010. © 2010 Wiley-Liss, Inc. [source] Skin wound healing in diabetic ,6 integrin-deficient miceAPMIS, Issue 10 2010JASPER N. JACOBSEN Jacobsen JN, Steffensen B, Häkkinen L, Krogfelt KA, Larjava HS. Skin wound healing in diabetic ,6 integrin-deficient mice. APMIS 2010; 118: 753,64. Integrin ,v,6 is a heterodimeric cell surface receptor, which is absent from the normal epithelium, but is expressed in wound-edge keratinocytes during re-epithelialization. However, the function of the ,v,6 integrin in wound repair remains unclear. Impaired wound healing in patients with diabetes constitutes a major clinical problem worldwide and has been associated with the accumulation of advanced glycated endproducts (AGEs) in the tissues. AGEs may account for aberrant interactions between integrin receptors and their extracellular matrix ligands such as fibronectin (FN). In this study, we compared healing of experimental excisional skin wounds in wild-type (WT) and ,6-knockout (,6,/,) mice with streptozotocin-induced diabetes. Results showed that diabetic ,6,/, mice had a significant delay in early wound closure rate compared with diabetic WT mice, suggesting that ,v,6 integrin may serve as a protective role in re-epithelialization of diabetic wounds. To mimic the glycosylated wound matrix, we generated a methylglyoxal (MG)-glycated variant of FN. Keratinocytes utilized ,v,6 and ,1 integrins for spreading on both non-glycated and FN-MG, but their spreading was reduced on FN-MG. These findings indicated that glycation of FN and possibly other integrin ligands could hamper keratinocyte interactions with the provisional matrix proteins during re-epithelialization of diabetic wounds. [source] | |||||||||||||