Integrins are essential receptors for the development and functioning of multicellular animals because they mediate cell adhesion and migration, and regulate cell proliferation and apoptosis. While integrin activation is known to require both ligand and talin binding and to correlate with cluster formation the activation mechanism and the detailed roles of the above processes have not yet been resolved. Using mathematical modeling and available experimental data we previously showed that integrin activation must involve a positive feedback via a signaling network [1]. We further characterized the proximal signaling network involving talin, PIPKI, and Dok1 [2], and showed that such a signaling network could indeed support integrin clustering [3]. Finally, we showed that partitioning integrins into clusters can enhance the sensitivity of cells to ligand [4].
Cells migrate in response to extracellular cues that signal through different receptor systems. In a separate line of work we wondered in how far the intracellular signalling responses would differ for these different cues. To this end we carried out a proteomic analysis and compared the protein content and phosphorylation state of pseudopods and cell body of cells that were exposed to either PDGF, LPA, or only fibronectin; fibronectin binds to integrins on cells [5].
PUBLICATIONS
Cells migrate in response to extracellular cues that signal through different receptor systems. In a separate line of work we wondered in how far the intracellular signalling responses would differ for these different cues. To this end we carried out a proteomic analysis and compared the protein content and phosphorylation state of pseudopods and cell body of cells that were exposed to either PDGF, LPA, or only fibronectin; fibronectin binds to integrins on cells [5].
PUBLICATIONS
- Iber D and Campbell ID, Integrin activation - the importance of a positive feedback. Bulletin of Mathematical Biology (2006); 68, 945-956
- Geier F, Fengos G and Iber D, A computational analysis of the dynamic roles of talin, Dok1, and PIPKI for integrin activation, Plos One (2011)
- Felizzi F and Iber D, Integrin clustering as a result of local membrane deformations and local signaling feedbacks, Physica A (2014) 408, 198-211
- Felizzi F and Iber D, Enhanced cellular sensitivity from partitioning the integrin receptors into multiple clusters. Phys Rev E (2013) 87: 012701
- Fengos G, Schmidt A, Martin K, Fluri E, Aebersold A, Iber D*, Pertz O* (* shared corresponding authors), Spatial proteomic and phospho-proteomic organization in three prototypical cell migration modes, Proteome Science (2014) 12: 23