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| Talin controls integrin activation |
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| Author(s): Calderwood DA |
| Source: BIOCHEMICAL SOCIETY TRANSACTIONS Volume: 32 Pages: 434-437 Part: Part 3 Published: JUN 2004 |
| Times Cited: 34 References: 49 |
| Abstract: 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-bincling protein, to integrin beta tails represents a final common step in integrin activation pathways. The major integrin-binding site lies within the talin FERM ((f) under bar our-point-one, (e) under bar zrin, (r) under bar adixin, (m) under bar oesin) 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. |
| Document Type: Proceedings Paper |
| Language: English |
| Reprint Address: Calderwood, DA (reprint author), Yale Univ, Sch Med, Dept Pharmacol, 333 Cedar St, New Haven, CT 06520 USA |
Addresses:
1. Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA |
| Publisher: PORTLAND PRESS, 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: 833LD |
| ISSN: 0300-5127 |
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