Bimodality in Ras signaling originates from processivity of the Ras activator SOS without deterministic bistability.
Sci Adv
; 10(25): eadi0707, 2024 Jun 21.
Article
in En
| MEDLINE
| ID: mdl-38905351
ABSTRACT
Ras is a small GTPase that is central to important functional decisions in diverse cell types. An important aspect of Ras signaling is its ability to exhibit bimodal or switch-like activity. We describe the total reconstitution of a receptor-mediated Ras activation-deactivation reaction catalyzed by SOS and p120-RasGAP on supported lipid membrane microarrays. The results reveal a bimodal Ras activation response, which is not a result of deterministic bistability but is rather driven by the distinct processivity of the Ras activator, SOS. Furthermore, the bimodal response is controlled by the condensation state of the scaffold protein, LAT, to which SOS is recruited. Processivity-driven bimodality leads to stochastic bursts of Ras activation even under strongly deactivating conditions. This behavior contrasts deterministic bistability and may be more resistant to pharmacological inhibition.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Ras Proteins
Limits:
Humans
Language:
En
Journal:
Sci Adv
Year:
2024
Document type:
Article
Affiliation country:
United States
Country of publication:
United States