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  • Control of SRC molecular dynamics encodes distinct cytoskeletal responses by specifying signaling pathway usage.

Control of SRC molecular dynamics encodes distinct cytoskeletal responses by specifying signaling pathway usage.

Journal of cell science (2021-01-27)
Adèle Kerjouan, Cyril Boyault, Christiane Oddou, Edwige Hiriart-Bryant, Alexei Grichine, Alexandra Kraut, Mylène Pezet, Martial Balland, Eva Faurobert, Isabelle Bonnet, Yohann Coute, Bertrand Fourcade, Corinne Albiges-Rizo, Olivier Destaing
ZUSAMMENFASSUNG

Upon activation by different transmembrane receptors, the same signaling protein can induce distinct cellular responses. A way to decipher the mechanisms of such pleiotropic signaling activity is to directly manipulate the decision-making activity that supports the selection between distinct cellular responses. We developed an optogenetic probe (optoSRC) to control SRC signaling, an example of a pleiotropic signaling node, and we demonstrated its ability to generate different acto-adhesive structures (lamellipodia or invadosomes) upon distinct spatio-temporal control of SRC kinase activity. The occurrence of each acto-adhesive structure was simply dictated by the dynamics of optoSRC nanoclusters in adhesive sites, which were dependent on the SH3 and Unique domains of the protein. The different decision-making events regulated by optoSRC dynamics induced distinct downstream signaling pathways, which we characterized using time-resolved proteomic and network analyses. Collectively, by manipulating the molecular mobility of SRC kinase activity, these experiments reveal the pleiotropy-encoding mechanism of SRC signaling.

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Roche
cOmplete, Mini, EDTA-freier Protease-Inhibitor-Cocktail, Protease Inhibitor Cocktail Tablets provided in a glass vial, Tablets provided in a glass vial
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Anti-Phosphotyrosin-Antikörper, Klon 4G10®, clone 4G10®, Upstate®, from mouse
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PP2, InSolution, ≥95%, 10 mM, reversible ATP-competitive inhibitor of the Src family of protein tyrosine kinases
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