Talin controls integrin activation.
Tight, dynamic control of the affinity of integrin adhesion receptors for their extracellular ligands (integrin activation) is essential for the development and functioning of multicellular organisms. Integrin activation is controlled by intracellular signals that, through their action on integrin cytoplasmic domains, induce conformational changes in integrin extracellular domains, resulting in increased affinity for the ligand. Recent results indicate that the binding of talin, a major actin-binding protein, to integrin beta tails represents a final common step in integrin activation pathways. The major integrin-binding site lies within the talin FERM (four-point-one, ezrin, radixin, moesin) domain, and binding occurs via a variant of the classical PTB domain (phosphotyrosine-binding domain)-NPxY interaction. Formation of this talin-integrin complex plays a critical role in integrin activation, since mutations, in either talin or integrin beta tails, which disrupt complex formation, inhibit integrin activation. Furthermore, use of RNA interference to knockdown talin expression selectively reveals that talin is essential for integrin activation in response to physiological agonists. Thus the association of the cytoskeletal protein talin with integrin beta cytoplasmic domains is a critical step during integrin activation, and regulation of this step may be a final common element in the signalling pathways that control integrin activation.
Calderwood
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DA
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520-8066, USA. david.calderwood@yale.edu
D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion; D003593:Cytoplasm / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D015398:Signal Transduction; D016608:Talin / Q000502:physiology*
D016023:Integrins; D008024:Ligands; D016608:Talin