Isoform-specific Ras signaling is growth factor dependent

Hood, Fiona E, Klinger, Bertram, Newlaczyl, Anna U, Sieber, Anja, Dorel, Mathurin, Oliver, Simon P, Coulson, Judy M ORCID: 0000-0003-2191-2001, Blüthgen, Nils and Prior, Ian A ORCID: 0000-0002-4055-5161 (2019) Isoform-specific Ras signaling is growth factor dependent. Molecular biology of the cell, 30 (9). pp. 1108-1117.

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Official URL: https://www.molbiolcell.org/doi/10.1091/mbc.E18-10...

Abstract

HRAS, NRAS and KRAS isoforms are almost identical proteins that are ubiquitously expressed and activate a common set of effectors. In vivo studies have revealed that they are not biologically redundant; however, the isoform-specificity of Ras signaling remains poorly understood. Using a novel panel of isogenic SW48 cell lines endogenously expressing wild type or G12V mutated activated Ras isoforms we have performed a detailed characterization of endogenous isoform-specific mutant Ras signaling. We find that despite displaying significant Ras activation, the downstream outputs of oncogenic Ras mutants are minimal in the absence of growth factor inputs. The lack of mutant KRAS-induced effector activation observed in SW48 cells appears to be representative of a broad panel of colon cancer cell lines harboring mutant KRAS. For MAP kinase pathway activation in KRAS mutant cells, the requirement for co-incident growth factor stimulation occurs at an early point in the Raf activation cycle. Finally, we find that Ras isoform-specific signaling was highly context dependent and did not conform to the dogma derived from ectopic expression studies.

Item Type:	Article
Uncontrolled Keywords:	Cell Line, Tumor, Humans, Cell Transformation, Neoplastic, ras Proteins, Intercellular Signaling Peptides and Proteins, Protein Isoforms, Signal Transduction, Mutation, Genes, ras
Depositing User:	Symplectic Admin
Date Deposited:	11 Apr 2019 12:27
Last Modified:	19 Jan 2023 00:54
DOI:	10.1091/mbc.e18-10-0676
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3036488