Characterisation of HRas local signal transduction networks using engineered site-specific exchange factors

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Title: Characterisation of HRas local signal transduction networks using engineered site-specific exchange factors
Authors: Herrero, Ana
Reis-Cardoso, Mariana
Jiménez-Gómez, Iñaki
Doherty, Carolanne
Kolch, Walter
Matallanas, David
et al.
Permanent link: http://hdl.handle.net/10197/9879
Date: 15-Jan-2018
Online since: 2019-04-10T09:45:55Z
Abstract: 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.
Funding Details: Science Foundation Ireland
Type of material: Journal Article
Publisher: Taylor & Francis
Journal: Small GTPases
Start page: 1
End page: 13
Keywords: RasLocalisationRas-GEFCDC25 domainOncogeneSignalling network
DOI: 10.1080/21541248.2017.1406434
Language: en
Status of Item: Peer reviewed
Appears in Collections:Medicine Research Collection

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