When cells come into contact with the extracellular matrix (ECM), they usually extend filopodia. Then, integrins located at the tip of filopodia bind to the ECM and initiate the formation of focal adhesions. Actin-rich lamellipodia are then generated as the cell spreads on the ECM . As the integrins bind to the ECM they become clustered in the plane of the cell membrane and associate with the cytoske-letal and signaling complex that promote the assembly of actin filaments. The reorganization of actin filaments into larger stress fibers in turn causes more clustering of integrins, thus enhancing the matrix binding and organization by integrins in a positive feedback system. As a consequence, the ECM proteins, integrins and cytoskeletal proteins assemble into aggregates on each side of the membrane, these aggregates being termed "focal adhesions". Several integrins have been found to associate laterally with caveolin-1, at least in primary cells (see Fig. 9.2) [17,18]. Although the biochemical nature of this interaction is not yet clear, inhibition of caveolin expression suppresses the formation of focal adhesions and actin stress fibers [5,17].
Integrins activate a variety of protein tyrosine kinases, including focal adhesion kinase (FAK), which may be recruited and acquire tyrosine kinase activity by its interaction with integrins. Subsequently, FAK can phosphorylate other cytoskeletal proteins. In addition to the activation of FAK, some b1 and av integrins can activate the tyrosine kinase Fyn and the adapter protein Shc. In this pathway, caveolin-1 appears to function as a membrane adaptor, which couples the integrin a-subunit to Fyn . In senescent HDFs, the inhibition of caveolin-1 expression can disrupt focal adhesion and actin stress fiber, most likely due to the de-phosphorylation of FAK . In NIH-3T3 cells, caveolin-2 undergoes Src-induced phosphorylation on Tyr19, which is localized near to the focal adhesion, and remains associated with the caveolae .
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.