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Functional atlas of the integrin adhesome

Abstract

A detailed depiction of the 'integrin adhesome', consisting of a complex network of 156 components linked together and modified by 690 interactions is presented. Different views of the network reveal several functional 'subnets' that are involved in switching on or off many of the molecular interactions within the network, consequently affecting cell adhesion, migration and cytoskeletal organization. Examination of the adhesome network motifs reveals a relatively small number of key motifs, dominated by three-component complexes in which a scaffolding molecule recruits both a signalling molecule and its downstream target. We discuss the role of the different network modules in regulating the structural and signalling functions of cell–matrix adhesions.

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Figure 1: Interactions between all intrinsic components of the adhesome and a grouped list of the associated components.
Figure 2: Interactions between functional families of adhesome components.
Figure 3: Actin–integrin subnet interconnecting the membrane receptors (mainly integrin) with actin.
Figure 4: Phosphorylation subnets mapping serine/threonine kinases and phosphatases (a) and tyrosine kinases and phosphatases (b).
Figure 5: GTPase, lipid and proteolytic subnets.
Figure 6: Phosphorylation switches regulating specific phosphotyrosine–SH2 domain interactions.
Figure 7: Network motifs of the adhesome.

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Acknowledgements

This project is funded in part by a National Institutes of Health (NIH) NanoMedicine Center for Mechanical Biology (GM-54508), Advanced Research Center Grant NYSTAR from New York State to R.I. and National Institute of General Medical Science (NIGMS) grant for the Cell Migration Consortium (NIH Grant U54 GM64346), and the United States-Israel Bionational Science Foundation. B.G. holds the Erwin Neter Professorial Chair in Cell and Tumor Biology.

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Zaidel-Bar, R., Itzkovitz, S., Ma'ayan, A. et al. Functional atlas of the integrin adhesome. Nat Cell Biol 9, 858–867 (2007). https://doi.org/10.1038/ncb0807-858

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