A directional switch of integrin signalling and a new anti-thrombotic strategy

• Published in: Nature (London) Vol. 503; no. 7474; pp. 131 - 135
• Main Authors: Shen, Bo, Zhao, Xiaojuan, O’Brien, Kelly A., Stojanovic-Terpo, Aleksandra, Delaney, M. Keegan, Kim, Kyungho, Cho, Jaehyung, Lam, Stephen C.-T., Du, Xiaoping
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.11.2013; Nature Publishing Group
• Subjects: 631/80/79/1236; Amino Acid Motifs; Amino Acid Sequence; Animals; Antithrombins - adverse effects; Antithrombins - pharmacology; Antithrombins - therapeutic use; Binding Sites; Bleeding Time; Blood clot; Blood platelets; Bone marrow; Cell interaction; Cell Polarity; Cytoplasm - metabolism; Drug therapy; GTP-Binding Protein alpha Subunits, G12-G13 - metabolism; Health aspects; Hemorrhage - chemically induced; Hemostasis; Humanities and Social Sciences; Humans; Integrin beta3 - chemistry; Integrin beta3 - genetics; Integrin beta3 - metabolism; Integrins; Integrins - chemistry; Integrins - deficiency; Integrins - genetics; Integrins - metabolism; letter; Ligands; Male; Mice; Mice, Inbred C57BL; Molecular Sequence Data; multidisciplinary; Physiological aspects; Platelet Glycoprotein GPIIb-IIIa Complex - metabolism; Protein Binding; Protein Structure, Tertiary; Science; Signal Transduction - drug effects; Stem cells; Talin - metabolism; Thromboembolism; Thrombosis; Thrombosis - drug therapy; Thrombosis - metabolism; Thrombosis - pathology; United States

The direction of integrin signalling is found to be determined by the coordinated and opposing binding waves of talin and Gα 13 to the same region of the integrin β 3 cytoplasmic domain at mutually exclusive but distinct sites, and a potent new anti-thrombotic drug that does not cause bleeding is de...