scholarly journals Molecular flux control encodes distinct cytoskeletal responses by specifying SRC signaling pathway usage

2019 ◽  
Author(s):  
Adèle Kerjouan ◽  
Cyril Boyault ◽  
Christiane Oddou ◽  
Edwige Hiriart-Bryant ◽  
Alexei Grichine ◽  
...  

AbstractMulti-domain signaling proteins sample numerous stimuli to coordinate distinct cellular responses. Understanding the mechanisms of their pleiotropic signaling activity requires to directly manipulate their activity of decision leading to distinct cellular responses. We developed an optogenetic probe, optoSRC, to control spatio-temporally the SRC kinase, a representative example of versatile signaling node, and challenge its ability to generate different cellular responses. Genesis of different local molecular fluxes of the same optoSRC to adhesion sites, was sufficient to trigger distinct and specific acto-adhesive responses. Collectively, this study reveals how hijacking the pleiotropy of SRC signaling by modulating in space and time subcellular molecular fluxes of active SRC kinases.

2021 ◽  
Vol 134 (2) ◽  
pp. jcs254599
Author(s):  
Adèle Kerjouan ◽  
Cyril Boyault ◽  
Christiane Oddou ◽  
Edwige Hiriart-Bryant ◽  
Alexei Grichine ◽  
...  

ABSTRACTUpon 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.


2012 ◽  
Vol 48 ◽  
pp. S108
Author(s):  
A.S. Ribeiro ◽  
A. Vieira ◽  
B. Sousa ◽  
A. Albergaria ◽  
R. Seruca ◽  
...  

2003 ◽  
Vol 278 (25) ◽  
pp. 22586-22595 ◽  
Author(s):  
Alpana Ray ◽  
Papiya Ray ◽  
Nicole Guthrie ◽  
Arvind Shakya ◽  
Deepak Kumar ◽  
...  

Author(s):  
Leanna R. Gentry ◽  
Andrei V. Karginov ◽  
Klaus M. Hahn ◽  
Channing J. Der
Keyword(s):  

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