Control of SRC molecular dynamics encodes distinct cytoskeletal responses by specifying signaling pathway usage.
J Cell Sci
; 134(2)2021 01 25.
Article
en En
| MEDLINE
| ID: mdl-33495358
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Citoesqueleto
/
Transducción de Señal
/
Familia-src Quinasas
/
Proteómica
Límite:
Animals
Idioma:
En
Revista:
J Cell Sci
Año:
2021
Tipo del documento:
Article
País de afiliación:
Francia