Tickling the tails: cytoplasmic domain proteins that regulate integrin alphaIIbbeta3 activation.
OBJECTIVE
Integrin alphaIIbbeta3 activation is essential for platelet aggregation and related hemostatic events. In recent years, intense effort has been put forward to understand the molecular mechanisms regulating platelet integrin alphaIIbbeta3 activation. Here we review the current models of alphaIIbbeta3 activation and highlight the potential regulatory roles of proteins that interact directly with the alphaIIbbeta3 cytoplasmic domains, with emphasis on the alphaIIb cytoplasmic domain binding protein, CIB1.


RESULTS
Mutational and crystallographic studies reveal the importance of integrin transmembrane and cytoplasmic domains in propagating bidirectional signaling events. Proteins that interact directly with the integrin cytoplasmic domains may play important roles in mediating these signaling events. Of particular interest is the interaction between CIB1 and the alphaIIb tail which may function to negatively regulate alphaIIbbeta3 activation. In addition, a number of CIB1 interacting proteins have been identified, including p21-activated kinase and serum-inducible kinase, which may act in concert with CIB1 to regulate platelet function.


CONCLUSIONS
Understanding the molecular mechanisms underlying integrin activation will be important in developing novel therapies to regulate platelet function in cardiovascular disease. Discussion of recent developments in elucidating the mechanism of integrin activation, with particular focus on the platelet integrin alphaIIbbeta3, is provided in this review.
Leisner
Tina M
TM
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA.
Yuan
Weiping
W
DeNofrio
Jan C
JC
Liu
Jun
J
Parise
Leslie V
LV
D003593:Cytoplasm / Q000737:chemistry*; D006801:Humans; D008565:Membrane Proteins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D008565:Membrane Proteins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex