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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. Bluthgen, Nils Prior, Ian A.
Hood, Fiona E.
Klinger, Bertram
Newlaczyl, Anna U.
Sieber, Anja
Dorel, Mathurin
Oliver, Simon P.
Coulson, Judy M.
Bluthgen, Nils
Prior, Ian A.
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Other Contributors
EPub Date
Publication Date
2019-04-11
Submitted Date
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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.
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), 1108-1117
Publisher
ASCB
Journal
Molecular Biology of the Cell
Research Unit
DOI
10.1091/mbc.E18-10-0676
PubMed ID
PubMed Central ID
Type
Article
Language
en
Description
Series/Report no.
ISSN
1059-1524
EISSN
1939-4586