Authors
Hood, Fiona E.Klinger, Bertram
Newlaczyl, Anna U.
Sieber, Anja
Dorel, Mathurin
Oliver, Simon P.
Coulson, Judy M.
Bluthgen, Nils
Prior, Ian A.
Affiliation
University of Liverpool; Universitätsmedizin Berlin; University of ChesterPublication Date
2019-04-11
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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.Citation
Hood, F. E., Klinger, B., Newlaczyl, A. U., Sieber, A., Dorel, M., Oliver, S., Coulson, J. M., Blüthgen, N., Prior, I. A. (2019). Isoform-specific Ras signaling is growth factor dependent. Molecular Biology of the Cell, 30(9), 1108-1117Publisher
ASCBJournal
Molecular Biology of the CellAdditional Links
https://www.molbiolcell.org/doi/abs/10.1091/mbc.E18-10-0676Type
ArticleLanguage
enISSN
1059-1524EISSN
1939-4586ae974a485f413a2113503eed53cd6c53
10.1091/mbc.E18-10-0676
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