Characterisation of HRas local signal transduction networks using engineered site-specific exchange factors.
CDC25 domain
Ras
Ras-GEF
localisation
oncogene
signalling network
Journal
Small GTPases
ISSN: 2154-1256
Titre abrégé: Small GTPases
Pays: United States
ID NLM: 101530974
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
pubmed:
28
11
2017
medline:
17
7
2021
entrez:
28
11
2017
Statut:
ppublish
Résumé
Ras GTPases convey signals from different types of membranes. At these locations, different Ras isoforms, interactors and regulators generate different biochemical signals and biological outputs. The study of Ras localisation-specific signal transduction networks has been hampered by our inability to specifically activate each of these Ras pools. Here, we describe a new set of site-specific tethered exchange factors, engineered by fusing the RasGRF1 CDC25 domain to sub-localisation-defining cues, whereby Ras pools at specific locations can be precisely activated. We show that the CDC25 domain has a high specificity for activating HRas but not NRas and KRas. This unexpected finding means that our constructs mainly activate endogenous HRas. Hence, their use enabled us to identify distinct pathways regulated by HRas in endomembranes and plasma membrane microdomains. Importantly, these new constructs unveil different patterns of HRas activity specified by their subcellular localisation. Overall, the targeted GEFs described herein constitute ideal tools for dissecting spatially-defined HRas biochemical and biological functions.
Identifiants
pubmed: 29172991
doi: 10.1080/21541248.2017.1406434
pmc: PMC7549619
doi:
Substances chimiques
ras-GRF1
0
HRAS protein, human
EC 3.6.5.2
Hras protein, mouse
EC 3.6.5.2
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
371-383Subventions
Organisme : Worldwide Cancer Research
ID : 15-0273
Pays : United Kingdom
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