%0 Journal Article
%T Focal Adhesion Kinases in Adhesion Structures and Disease
%A Pierre P. Eleniste
%A Angela Bruzzaniti
%J Journal of Signal Transduction
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/296450
%X Cell adhesion to the extracellular matrix (ECM) is essential for cell migration, proliferation, and embryonic development. Cells can contact the ECM through a wide range of matrix contact structures such as focal adhesions, podosomes, and invadopodia. Although they are different in structural design and basic function, they share common remodeling proteins such as integrins, talin, paxillin, and the tyrosine kinases FAK, Pyk2, and Src. In this paper, we compare and contrast the basic organization and role of focal adhesions, podosomes, and invadopodia in different cells. In addition, we discuss the role of the tyrosine kinases, FAK, Pyk2, and Src, which are critical for the function of the different adhesion structures. Finally, we discuss the essential role of these tyrosine kinases from the perspective of human diseases. 1. Introduction The extracellular matrix (ECM) is an insoluble supra-structure comprised of a variety of matrix components including fibronectin, glycosaminoglycans, chrondronectin, osteonectin, collagens, laminin, proteoglycans, and growth factors [1¨C6]. The ECM provides the scaffold for cell attachment which is necessary for several diverse cellular activities, including cytoskeletal remodeling, polarization, differentiation, migration, and invasion [7¨C9]. Binding to the ECM is regulated by various signaling pathways that control the assembly and disassembly of three distinct, but functionally related actin and integrin-containing adhesion structures known as focal adhesions, podosomes, and invadopodia. In this review, we will discuss our current understanding of the similarities and differences between focal adhesions, podosomes, and invadopodia. We also will highlight several important tyrosine kinases and other signaling proteins that are known to control the formation and function of these adhesion structures, and we will discuss their role in pathophysiology. 2. Focal Adhesions Focal adhesion formation and turnover has been used as a model system for understanding the mechanisms of cellular adhesion. Although focal adhesions, podosomes, and invadopodia share common signaling proteins, they are distinct in cellular architecture and function (summarized in Table 1). Focal adhesions, also known as ˇ°focal contacts,ˇ± were identified over 30 years ago by electron microscopy and described as electron-dense plaques associated with actin filament bundles [10]. Focal adhesions can be considered to be large protein assembly complexes that spread mechanical forces from sites of cell adhesion to the cell body. In addition, focal adhesions
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