Integrin Activation

Abstract

SummaryIntegrins are cell surface adhesion receptors that participate in a variety of important processes throughout the vasculature. Here we summarize some recent findings on the regulation of integrin mediated cellular adhesion. Particular emphasis is placed on the regulation of integrin affinity for ligand (activation), although this is just one mechanism by which regulation of integrin-dependent cell adhesion can occur. Also discussed are recent observations on the structural basis of integrin activation, the role of the cytoplasmic domain in integrin affinity regulation, and potential mechanisms by which activation signals are propagated from integrin cytoplasmic domains to the extracellular ligand binding domain.

Sustained integrin ligation involves extracellular free sulfhydryls and enzymatically catalyzed disulfide exchange

“…Type I collagen prepared for use in flow cytometry was described previously. 25 The triple-helical peptide, collagenrelated peptide Gly-Lys-Hyp-(Gly-Pro-Hyp) 10 -Gly-Lys-Hyp-Gly (CRP), was synthesized and cross-linked by means of its lysyl residues to yield CRP-XL, as described previously. 26 Platelet agonists used in aggregation studies were from Bio/Data (Horsham, PA).…”

“…In recent years, the posited mechanism has been the allosteric conformational changes occurring in the integrin receptor, both in response to cellular events that switch the receptor from low to high affinity (inside-out signaling) and external events that relay information about occupancy of the receptor (outside-in signaling). [6][7][8][9] Although information about the nature of the changes in conformation is slowly emerging (for review, see Woodside et al 10 ) and consequent changes in intracellular interactions are widely documented, [10][11][12][13] the molecular mechanism regulating such changes, particularly on the exofacial domain, has not been elucidated. We previously reported that extracellular sulfhydryls participate in conformational changes triggered by interaction of the platelet integrin ␣ 2 ␤ 1 with its natural ligand collagen.…”

P-selectin activates integrin-mediated colon carcinoma cell adhesion to fibronectin

“…In leukocytes, after selectin-mediated cell tethering to the blood vessel wall, integrin involvement is required to produce the stable adhesion for their extravasation [18]. Therefore, we tested the hypothesis that P-selectin binding could induce activation of β1 integrin, a mechanism by which increased cell adhesion may occur through a change in integrin conformation increasing its ligand affinity or/and through integrin clustering [11,45,46]. The ability of P-selectin to induce a conformational change resulting in β1-integrin activation was analyzed by flow cytometry using two different anti-β1 integrin mAbs: HUTS-21, which recognizes the activation-dependent epitope of β1 integrin [47] and K20 which reacts with total β1 integrin.…”

14-3-3ζ Mediates Integrin-induced Activation of Cdc42 and Rac

“…Many integrins cannot bind extracellular ligands until intracellular signals "activate" the integrins by inducing clustering or conformational changes (41). Activation can be induced by signals transmitted across a variety of cytokine or adhesion receptors (41).…”

“…Activation can be induced by signals transmitted across a variety of cytokine or adhesion receptors (41). In platelets, activation is induced by signals transmitted as GP Ib-IX binds vWf (42).…”