Proteomics

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Time-resolved phosphotyrosine-proteome of Src signaling

ABSTRACT: Intracellular signaling nodes can sample multiple inputs and induce different cellular outputs. High combinatorial between their numerous potential conformational intermediaries having distinct enzymatic activities and/or repertoire of partners makes it challenging to determine their dynamic coding molecularly. We have combined protein engineering with optogenetic to investigate coding functions of specific intermediaries of the kinase Src, a representative example of versatile signaling node. Optogenetic is used to generate local flux of specific Src intermediaries, as Src dimers, into adhesion sites. Modulations of this molecular flux are sufficient to code different Src signaling pathways and Src-dependent cellular outputs implicated in migration or invasion. This response selectivity is based on the ability for each flux of Src conformational intermediary to generate distinct Src signaling waves in protein-protein interaction networks revealed by time-resolved analysis of phosphotyrosine-proteome. Thus, the pleiotropy of a signaling node is molecularly coded by modulation of its local fluxes of specific conformational intermediaries.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Canis Familiaris (dog) (canis Lupus Familiaris)

SUBMITTER: Yohann Couté  

LAB HEAD: Virginie Brun

PROVIDER: PXD008534 | Pride | 2021-02-03

REPOSITORIES: Pride

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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 struc  ...[more]

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