The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
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]
In the citing paper
“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]
Citations
Cites
Inositol trisphosphate and diacylglycerol as second messengers
Berridge, M. J. (1984) · Biochemical Journal · doi:10.1042/bj2200345 · Cited by 3,506
G proteins and dual control of adenylate cyclase
Gilman, A. G. (1984) · Cell · doi:10.1016/0092-8674(84)90336-2 · Cited by 1,772
Mechanism of activation of a human oncogene
Tabin, C. J., Bradley, S. M., Bargmann, C. I., Weinberg, R. A., Papageorge, A. G., Scolnick, E. M., Dhar, R., Lowy, D. R., & Chang, E. H. (1982) · Nature · doi:10.1038/300143a0 · Cited by 1,393
Reddy, E. P., Reynolds, R. K., Santos, E., & Barbacid, M. (1982) · Nature · doi:10.1038/300149a0 · Cited by 1,391
Intracellular phospholipases A
van den BOSCH, H. (1980) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(80)90574-x · Cited by 982
Human EJ bladder carcinoma oncogene is homologue of Harvey sarcoma virus ras gene
Parada, L. F., Tabin, C. J., Shih, C., & Weinberg, R. A. (1982) · Nature · doi:10.1038/297474a0 · Cited by 947
Requirement for ras proto-oncogene function during serum-stimulated growth of NIH 3T3 cells
Mulcahy, L. S., Smith, M. R., & Stacey, D. W. (1985) · Nature · doi:10.1038/313241a0 · Cited by 851
Expression of Cellular Oncogenes in Human Malignancies
Slamon, D. J., deKernion, J. B., Verma, I. M., & Cline, M. J. (1984) · Science · doi:10.1126/science.6538699 · Cited by 810
Zarbl, H., Sukumar, S. V., Arthur, A. V., Martı́n-Zanca, D., & Barbacid, M. (1985) · Nature · doi:10.1038/315382a0 · Cited by 807
Der, C. J., Krontiris, T. G., & Cooper, G. M. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.11.3637 · Cited by 793
Microinjection of the ras oncogene protein into PC12 cells induces morphological differentiation
Bar‐Sagi, D., & Feramisco, J. R. (1985) · Cell · doi:10.1016/0092-8674(85)90280-6 · Cited by 733
Self-citationComparative biochemical properties of normal and activated human ras p21 protein
McGrath, J. P., Capon, D. J., Goeddel, D. V., & Levinson, A. D. (1984) · Nature · doi:10.1038/310644a0 · Cited by 699
Chang, E. H., Furth, M. E., Scolnick, E. M., & Lowy, D. R. (1982) · Nature · doi:10.1038/297479a0 · Cited by 588
The p21 ras C-terminus is required for transformation and membrane association
Willumsen, B. M., Christensen, A., Hubbert, N. L., Papageorge, A. G., & Lowy, D. R. (1984) · Nature · doi:10.1038/310583a0 · Cited by 584
Intrinsic GTPase activity distinguishes normal and oncogenic ras p21 molecules.
Gibbs, W. W., Sigal, I. S., Poe, M., & Scolnick, E. M. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.18.5704 · Cited by 580
Activation of Ki-ras2 gene in human colon and lung carcinomas by two different point mutations
Capon, D. J., Seeburg, P. H., McGrath, J. P., Hayflick, J. S., Edman, U., Levinson, A. D., & Goeddel, D. V. (1983) · Nature · doi:10.1038/304507a0 · Cited by 535
The product of ras is a GTPase and the T24 oncogenic mutant is deficient in this activity
Sweet, R. W., Yokoyama, S., Kamata, T., Feramisco, J. R., Rosenberg, M. J., & Gross, M. S. (1984) · Nature · doi:10.1038/311273a0 · Cited by 532
Self-citationNakamura, T., & Ui, M. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)83662-1 · Cited by 507
The concept of lipid domains in membranes.
Karnovsky, M. J., Kleinfeld, A. M., Hoover, R. L., & Klausner, R. D. (1982) · The Journal of Cell Biology · doi:10.1083/jcb.94.1.1 · Cited by 470
Noda, M., Ko, M. S. H., Ogura, A., Liu, D. G., Amano, T., Takano, T., & Ikawa, Y. (1985) · Nature · doi:10.1038/318073a0 · Cited by 449
Ras -Transformed Cells: Altered Levels of Phosphatidylinositol-4,5-Bisphosphate and Catabolites
Fleischman, L. F., Chahwala, S. B., & Cantley, L. C. (1986) · Science · doi:10.1126/science.3001936 · Cited by 422
Inhibition of receptor-mediated release of arachidonic acid by pertussis toxin
Bokoch, G., & Gilman, A. G. (1984) · Cell · doi:10.1016/0092-8674(84)90008-4 · Cited by 422
Hagag, N. G., Halegoua, S., & Viola, M. V. (1986) · Nature · doi:10.1038/319680a0 · Cited by 419
Willingham, M. C., Pastan, I. H., Shih, T. Y., & Scolnick, E. M. (1980) · Cell · doi:10.1016/0092-8674(80)90091-4 · Cited by 398
Growth factors immediately raise cytoplasmic free Ca2+ in human fibroblasts.
Moolenaar, W. H., Tertoolen, L. G. J., & de Laat, S. W. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)39690-4 · Cited by 392
Three human transforming genes are related to the viral ras oncogenes.
Shimizu, K., Goldfarb, M. P., Suard, Y. M. L., Perucho, M., Li, Y., Kamata, T., Feramisco, J. R., Stavnezer, E., Fogh, J. M., & Wigler, M. H. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.8.2112 · Cited by 389
Self-citationFeramisco, J. R., Gross, M. S., Kamata, T., Rosenberg, M. J., & Sweet, R. W. (1984) · Cell · doi:10.1016/0092-8674(84)90531-2 · Cited by 389
Self-citationSteinman, R. M., Silver, J., & Cohn, Z. A. (1974) · The Journal of Cell Biology · doi:10.1083/jcb.63.3.949 · Cited by 385
Transformation of NIH 3T3 cells by microinjection of Ha-ras p21 protein
Stacey, D. W., & Kung, H. (1984) · Nature · doi:10.1038/310508a0 · Cited by 380
The Biosynthesis and Metabolism of Prostaglandins
Lands, W. E. M. (1979) · Annual Review of Physiology · doi:10.1146/annurev.ph.41.030179.003221 · Cited by 375
Structure of the Ki-ras gene of the human lung carcinoma cell line Calu-1
Shimizu, K., Birnbaum, D., Ruley, M. A., Fasano, O., Suard, Y. M. L., Edlund, L., Taparowsky, E. J., Goldfarb, M. P., & Wigler, M. H. (1983) · Nature · doi:10.1038/304497a0 · Cited by 373
Chiou, C. Y., & Malagodi, M. H. (1975) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1975.tb07359.x · Cited by 346
Rapid stimulation of pinocytosis in human carcinoma cells A-431 by epidermal growth factor.
Haigler, H. T., McKanna, J. A., & Cohen, S. (1979) · The Journal of Cell Biology · doi:10.1083/jcb.83.1.82 · Cited by 330
Scolnick, E. M., Papageorge, A. G., & Shih, T. Y. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.10.5355 · Cited by 302
Rapid induction of morphological changes in human carcinoma cells A-431 by epidermal growth factors.
Chinkers, M., McKanna, J. A., & Cohen, S. (1979) · The Journal of Cell Biology · doi:10.1083/jcb.83.1.260 · Cited by 296
McKean, M. L., Smith, J. B., & Silver, M. J. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)69832-7 · Cited by 217
Kamata, T., & Feramisco, J. R. (1984) · Nature · doi:10.1038/310147a0 · Cited by 199
Self-citationKasid, A., Lippman, M. E., Papageorge, A. G., Lowy, D. R., & Gelmann, E. P. (1985) · Science · doi:10.1126/science.4039465 · Cited by 185
Surface functions during mitosis I: Phagocytosis, pinocytosis and mobility of surface-bound ConA
Berlin, R. D., Oliver, J. M., & Walter, R. J. (1978) · Cell · doi:10.1016/0092-8674(78)90002-8 · Cited by 184
Korchak, H. M., Rutherford, L. E., & Weissmann, G. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)43010-9 · Cited by 174
Davies, P., & Ross, R. (1978) · The Journal of Cell Biology · doi:10.1083/jcb.79.3.663 · Cited by 173
Brunk, U. T., Schellens, J. H. M., & Westermark, B. (1976) · Experimental Cell Research · doi:10.1016/0014-4827(76)90266-4 · Cited by 166
The role of calcium in lymphocyte proliferation. (An interpretive review)
Lichtman, A., Segel, G., & Lichtman, M. A. (1983) · Blood · doi:10.1182/blood.v61.3.413.413 · Cited by 151
Connolly, J., Greene, L., Viscarello, R. R., & Riley, W. (1979) · The Journal of Cell Biology · doi:10.1083/jcb.82.3.820 · Cited by 144
Ras p21 proteins with high or low GTPase activity can efficiently transform NIH3T3 cells
Lacal, J. C., Srivastava, S. K., Anderson, P. S., & Aaronson, S. A. (1986) · Cell · doi:10.1016/0092-8674(86)90270-9 · Cited by 111
Cockcroft, S., Bennett, J. P., & Gomperts, B. D. (1981) · Biochemical Journal · doi:10.1042/bj2000501 · Cited by 110
Purification and Characterization of Human H-ras Proteins Expressed in Escherichia coli
Gross, M. S., Sweet, R. W., Sathe, G. M., Yokoyama, S., Fasano, O., Goldfarb, M. P., Wigler, M. H., & Rosenberg, M. J. (1985) · Molecular and Cellular Biology · doi:10.1128/mcb.5.5.1015-1024.1985 · Cited by 105
[48] Fluorescent localization of contractile proteins in tissue culture cells
Wang, K., Feramisco, J. R., & Ash, J. F. (1982) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(82)85050-7 · Cited by 95
Self-citationShier, W. T., & Durkin, J. P. (1982) · Journal of Cellular Physiology · doi:10.1002/jcp.1041120204 · Cited by 91
Goshima, K., Masuda, A., & Owaribe, K. (1984) · The Journal of Cell Biology · doi:10.1083/jcb.98.3.801 · Cited by 86
Davis, B. H., Walter, R. J., Pearson, C. B., Becker, E. L., & Oliver, J. M. (1982) · PubMed Central · Cited by 80
Efflux of 45CA2+ from human fibroblasts in response to serum or growth factors
Owen, N. E., & Villereal, M. L. (1983) · Journal of Cellular Physiology · doi:10.1002/jcp.1041170105 · Cited by 66
[33] Use of horseradish peroxidase and fluorescent dextrans to study fluid pinocytosis in leukocytes
Oliver, J. M., Berlin, R. D., & Davis, B. H. (1984) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(84)08100-3 · Cited by 52
Biochemical characterization of polypeptides encoded by mutated human Ha-ras1 genes.
Colby, W. W., Hayflick, J. S., Clark, S. G., & Levinson, A. D. (1986) · Molecular and Cellular Biology · doi:10.1128/mcb.6.2.730 · Cited by 42
Vicentini, L. M., Miller, R. J., & Villereal, M. L. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)39814-9 · Cited by 36
Reversible pinocytosis in polymorphonuclear leukocytes.
Daukas, G., Lauffenburger, D. A., & Zigmond, S. H. (1983) · The Journal of Cell Biology · doi:10.1083/jcb.96.6.1642 · Cited by 34
Surface functions during mitosis in rat basophilic leukemia cells.
Oliver, J. M., Seagrave, J., Pfeiffer, J. R., Feibig, M. L., & Deanin, G. G. (1985) · The Journal of Cell Biology · doi:10.1083/jcb.101.6.2156 · Cited by 31
Membrane economics in endocytic systems
Duncan, R., & Pratten, M. K. (1977) · Journal of Theoretical Biology · doi:10.1016/0022-5193(77)90241-7 · Cited by 31
Balk, S. D., Riley, T. M., Gunther, H. S., & Morisi, A. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.17.5781 · Cited by 30
Akyempon, C. K., & Roufogalis, B. D. (1982) · Cell Calcium · doi:10.1016/0143-4160(82)90034-3 · Cited by 15
Flagged first, then by citations
Research works printed but not linked: 2
- ALLISON, A.C., SYMPOSIA OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY 28: 419 (1974).
- McClure, D. B., Cold Spring Harbor Conferences on Cell Proliferation 9: 345 (1982).
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Takai, Y., Sasaki, T., & Matozaki, T. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.1.153 · Cited by 2,511
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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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