Article

Ma YQ, Qin J, Wu C et al.Kindlin-2 (Mig-2): a co-activator of beta3 integrins. J Cell Biol 181:439-446

Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH 44195, USA.
The Journal of Cell Biology (Impact Factor: 9.69). 06/2008; 181(3):439-46. DOI: 10.1083/jcb.200710196
Source: PubMed

ABSTRACT Integrin activation is essential for dynamically linking the extracellular environment and cytoskeletal/signaling networks. Activation is controlled by integrins' short cytoplasmic tails (CTs). It is widely accepted that the head domain of talin (talin-H) can mediate integrin activation by binding to two sites in integrin beta's CT; in integrin beta(3) this is an NPLY(747) motif and the membrane-proximal region. Here, we show that the C-terminal region of integrin beta(3) CT, composed of a conserved TS(752)T region and NITY(759) motif, supports integrin activation by binding to a cytosolic binding partner, kindlin-2, a widely distributed PTB domain protein. Co-transfection of kindlin-2 with talin-H results in a synergistic enhancement of integrin alpha(IIb)beta(3) activation. Furthermore, siRNA knockdown of endogenous kindlin-2 impairs talin-induced alpha(IIb)beta(3) activation in transfected CHO cells and blunts alpha(v)beta(3)-mediated adhesion and migration of endothelial cells. Our results thus identify kindlin-2 as a novel regulator of integrin activation; it functions as a coactivator.

0 Followers
 · 
141 Views
  • Source
    • "This interaction is known to be of a slip bond type as opposed to fibronectin–a5b1 interactions, which is catch bond (Litvinov et al., 2011). A slip bond has a rate of breakage that exponentially increases with applied force, whereas catch bonds strengthen with the application of force (Thomas, 2008). "
  • Source
    • "This interaction is known to be of a slip bond type as opposed to fibronectin–a5b1 interactions, which is catch bond (Litvinov et al., 2011). A slip bond has a rate of breakage that exponentially increases with applied force, whereas catch bonds strengthen with the application of force (Thomas, 2008). "
  • Source
    • "This interaction is known to be of a slip bond type as opposed to fibronectin–a5b1 interactions, which is catch bond (Litvinov et al., 2011). A slip bond has a rate of breakage that exponentially increases with applied force, whereas catch bonds strengthen with the application of force (Thomas, 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cells contain several mechanosensing components that transduce mechanical signals into biochemical cascades. During cell-ECM adhesion, a complex network of molecules mechanically couples the extracellular matrix (ECM), cytoskeleton, and nucleoskeleton. The network comprises transmembrane receptor proteins and focal adhesions, which link the ECM and cytoskeleton. Additionally, recently identified protein complexes extend this linkage to the nucleus by linking the cytoskeleton and the nucleoskeleton. Despite numerous studies in this field, due to the complexity of this network, our knowledge of the mechanisms of cell-ECM adhesion at the molecular level remains remarkably incomplete. Herein, we present a review of the structures of key molecules involved in cell-ECM adhesion, along with an evaluation of their predicted roles in mechanical sensing. Additionally, specific binding events prompted by force-induced conformational changes of each molecule are discussed. Finally, we propose a model for the biomechanical events prominent in cell-ECM adhesion.
    International review of cell and molecular biology 04/2014; 310. DOI:10.1016/B978-0-12-800180-6.00005-0. · 4.52 Impact Factor
Show more

Preview (3 Sources)

Download
2 Downloads
Available from