RECENT INSIGHTS INTO LIGAND-BINDING, ACTIVATION AND SIGNALING BY INTEGRIN ADHESION RECEPTORS

In recent years, analyses of the structure and function of membrane-in tercalated adhesion molecules have shown them to play key roles in det ermining cellular phentoype. As expected, adhesion has an important ro le in regulating cellular positioning, but there is also compelling ev idence that information transduced via adhesion molecules affects the differentiation status of cells. Cell surface adhesion molecules can b e classified into a number of gene families, including immunoglobulins , cadherins, selectins, proteoglycans, and integrins. All of these typ es of molecule are co-expressed on most cells; and therefore the overa ll contribution of adhesion to cell phenotype is likely to be a net ef fect of the individual contributions of each of these groups. In this review, we will focus on the role of the integrins, which appear to be particularly important mediators of cell migration and adhesion-depen dent intracellular signalling. A great deal is now known about the ext racellular faces of integrins, including their structure and ligand-bi nding mechanisms, and in recent years, our knowledge of integrin-depen dent signalling via cytoplasmic domains has improved considerably. An emerging picture is one of a dynamic family of receptors than can be e xpressed in different states of activation. Alterations in activity ar e apparently mediated by conformational changes that can be induced fr om both outside and inside cells. In rum, these changes in activity ha ve concomitant consequences for adhesion and signalling.