Constitutively Active 1 RAS in S. Pombe Causes Persistent Cdc42 Signalling But Only Transient MAPK Activation

2018 ◽  
Author(s):  
Emma J. Kelsall ◽  
Ábel Vértesy ◽  
Kees Straatman ◽  
Mishal Tariq ◽  
Raquel Gadea ◽  
...  
Keyword(s):  
Mapk Activation ◽  
Constitutively Active

scholarly journals Constitutively active RAS in S. pombe causes persistent Cdc42 signalling but only transient MAPK activation

2018 ◽  
Author(s):  
Emma J Kelsall ◽  
Abel Vertesy ◽  
Kees Straatman ◽  
Mishal Tariq ◽  
Raquel Gadea ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Fission Yeast ◽  
Negative Feedback ◽  
Deletion Mutant ◽  
Small Gtpase ◽  
Mapk Activation ◽  
Activation Dynamics ◽  
Feedback Circuits ◽  
Pheromone Signalling ◽  
Constitutively Active

The small GTPase RAS is a signalling hub for many pathways and oncogenic human RAS mutations are assumed to over-activate all of its downstream pathways. We tested this assumption in fission yeast, where, RAS-mediated pheromone signalling (PS) activates the MAPKSpk1 and Cdc42 pathways. Unexpectedly, we found that constitutively active Ras1.G17V induced immediate but only transient MAPKSpk1 activation, whilst Cdc42 activation persisted. Immediate but transient MAPKSpk1 activation was also seen in the deletion mutant of Cdc42-GEFScd1, a Cdc42 activator. We built a mathematical model using PS negative-feedback circuits and competition between the two Ras1 effectors, MAPKKKByr2 and Cdc42-GEFScd1. The model robustly predicted the MAPKSpk1 activation dynamics of an additional 21 PS mutants. Supporting the model, we showed that a recombinant Cdc42-GEFScd1 fragment competes with MAPKKKByr2 for Ras1 binding. Our study has established a concept that the constitutively active RAS propagates differently to downstream pathways where the system prevents MAPK overactivation.

Constitutively active phosphatidlyinositol 3-kinase (Pl 3-K) and Akt are sufficient to stimulate NHE3: Insights in mechanisms of NHE3 stimulation

2001 ◽  
Vol 120 (5) ◽  
pp. A696-A696
Author(s):  
W KWON ◽  
D JOHNS ◽  
M CAVET ◽  
J PARK ◽  
P TSICHLIS ◽  
...  
Keyword(s):  
Constitutively Active

Antibodies directed against retained intron 4 of the constitutively active CCK-2 receptor bind to a tumour-specific epitope

2001 ◽  
Vol 120 (5) ◽  
pp. A496-A496 ◽  
Author(s):  
P CLARKE ◽  
S GRIMES ◽  
D MCWILLIAMS ◽  
W KLEIE ◽  
K KHAN ◽  
...  
Keyword(s):  
Specific Epitope ◽  
Retained Intron ◽  
Intron 4 ◽  
Constitutively Active
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