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Induction of Membrane Ruffling and Fluid-Phase Pinocytosis in Quiescent Fibroblasts by ras Proteins
Abstract
Expression of the ras oncogene is thought to be one of the contributing events in the initiation of certain types of human cancer. To determine the cellular activities that are directly triggered by ras proteins, the early consequences of microinjection of the human H- ras proteins into quiescent rat embryo fibroblasts were investigated. Within 30 minutes to 1 hour after injection, cells show a marked increase in surface ruffles and fluid-phase pinocytosis. The rapid enhancement of membrane ruffling and pinocytosis is induced by both the proto-oncogenic and the oncogenic forms of the H- ras protein. The effects produced by the oncogenic protein persist for more than 15 hours after injection, whereas the effects of the proto-oncogenic protein are short-lived, being restricted to a 3-hour interval after injection. The stimulatory effect of the ras oncogene protein on ruffling and pinocytosis is dependent on the amount of injected protein and is accompanied by an apparent stimulation of phospholipase A 2 activity. These rapid changes in cell membrane activities induced by ras proteins may represent primary events in the mechanism of action of ras proteins.
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“The ability to stimulate macropinocytosis, a regulated form of endocytosis, is a distinctive feature of KRAS∗ activation,13 and PDAC cells harboring KRAS∗ rely on increased levels of macropinocytosis for nutrient salvaging to sustain uncontrolled cell growth.14”
From Therapeutic targeting of syndecan-1 axis overcomes acquired resistance to KRAS-targeted therapy in gastrointestinal cancers (2025) · cites this paper as [13]
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“The autophagy-MHC-I relationship provides mechanistic insight to functional genomics studies in mice, which have also linked autophagy and immune evasion in PDAC228.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [228]
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Metadata
- Authors
- Bar-Sagi, D., & Feramisco, J. R.
- Affiliations
- Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724
- Cold Spring Harbor Laboratory (US)
- Venue
- Science
- Published
- 1986-09-05
- Volume
- 233
- Issue
- 4768
- Pages
- 1061-1068
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1969560454
- Cited by
- 734
- References
- 60
- Citations by year
- 2026: 6 · 2025: 15 · 2024: 17 · 2023: 23 · 2022: 17 · 2021: 21 · 2020: 17 · 2019: 25 · 2018: 23 · 2017: 19 · 2016: 14 · 2015: 25 · 2014: 14 · 2013: 11 · 2012: 5
- FWCI
- 14.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA39811, CA07896)
- National Institute of General Medical Sciences (GM 28277)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- H-Ras, oncogenic Ras, ruffles, fluid-phase pinocytosis, quiescent fibroblasts, phospholipase A2, cell membrane dynamics, microinjection, tumor initiation
- MeSH terms
- Animals, Cell Cycle, Cell Membrane, Cells, Cultured, Culture Media, DNA, Humans, Microinjections, Oncogene Proteins, Viral, Phospholipases A, Phospholipids, Pinocytosis, Time Factors, GTP-Binding Proteins, Rats, Phospholipases A2
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