Published online
doi:10.1083/jcb.200710196
The Journal of Cell Biology, Vol. 181, No. 3, 439-446
The Rockefeller University Press, 0021-9525 $30.00
© Ma et al.
Kindlin-2 (Mig-2): a co-activator of β3 integrins
Yan-Qing Ma1,
Jun Qin1,
Chuanyue Wu2, and
Edward F. Plow1
1 Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH 44195
2 Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261
Correspondence to Edward F. Plow: plowe{at}ccf.org
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 β's CT; in integrin β3 this is an NPLY747 motif and the membrane-proximal region. Here, we show that the C-terminal region of integrin β3 CT, composed of a conserved TS752T region and NITY759 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
IIbβ3 activation. Furthermore, siRNA knockdown of endogenous kindlin-2 impairs talin-induced
IIbβ3 activation in transfected CHO cells and blunts
vβ3-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.
Abbreviations used in this paper: CT, cytoplasmic tail; HUVEC, human umbilical vein endothelial cell; talin-H, talin head domain.
© 2008 Ma et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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