Brian G. Petrich
Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla, California, USA
Integrins are heterodimeric adhesion receptors essential for metazoan life. In addition to mediating cell-extracellular matrix and cell-cell interactions, integrins are bona fide signalling receptors in that they transmit information in both directions across the plasma membrane. The affinity of integrins for extracellular ligands is regulated through a process termed integrin activation or “inside-out signalling”. On the other hand, ligand binding to integrins can induce the recruitment and activation of a number of enzymes and adaptors such as pp125FAK and Src family kinases, to initiate “outside-in signalling”. Intensive investigation into the mechanisms of integrin signalling has revealed many of the key players; amongst these, one of the most important is talin. Our understanding of how many of these molecules interact is now understood at the atomic level thanks to detailed structural studies. Indeed structural information and model cell systems have provided unique opportunities to dissect the molecular mechanisms of many aspects of integrin signalling. Recent studies have begun testing the biological significance of these mechanisms using in-vivo models, particular genetically modified mice. The generation and characterisation of in-vivo models to study integrin signalling has provided valuable information into the functional significance of integrin signalling in fundamental physiological processes as well as within the context of human disease. Here, I will review recent insights that have been gained into integrin signalling through the use of genetically modified mice focusing on integrin αIIbβ3 (GPIIb-IIIa) and the regulation of its function in haemostasis and thrombosis.
thrombosis, integrins, Adhesion receptors
Emmanouil Chavakis1; Eun Young Choi2; Triantafyllos Chavakis2
Thromb Haemost 2009 102 2: 191-197
Ok-Nam Bae*1, Young-Dae Kim*1, Kyung-Min Lim1,2, Ji-Yoon Noh1, Seung-Min Chung1, Keunyoung Kim1, Suyoung Hong1, Sue Shin3, Jong-Hyun Yoon3, Jin-Ho Chung1
Thromb Haemost 2008 100 1: 52-59
Phlebologie 2003 32 2: 29-36
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