Abstract
Serum and growth factors can increase the proportion of Ras in the active guanosine triphosphate (GTP)-bound form. Growth factors might stimulate guanine nucleotide exchange or decrease the activity of the guanosine triphosphatase-activating proteins GAP and neurofibromin (NF1). In NIH 3T3 cells that overexpress the mutant Ras protein His 116 , which releases bound guanine nucleotide at a constitutively high rate and retains sensitivity to GAP and NF1, the proportion of GTP bound to the His 116 protein was not altered by serum or platelet-derived growth factor. However, these mitogens increased the proportion of Ras in the GTP-bound form in cells that overexpressed control Ras proteins with a normal intrinsic rate of guanine nucleotide release. The amount of GTP-bound His 116 or control Ras proteins was higher in cells at low density than in cells at high density, which have more GAP-like activity. The lower proportion of GTP-bound Ras in NIH 3T3 cells at high density may result from increased GAP-like activity. By contrast, serum and platelet-derived growth factors appear to stimulate guanine nucleotide exchange.
References
34
Referenced
61
10.1016/0092-8674(90)90151-4
10.1038/348503a0
10.1038/348125a0
-
BROEK, D, THE SACCHAROMYCES-CEREVISIAE CDC25 GENE-PRODUCT REGULATES THE RAS/ADENYLATE CYCLASE PATHWAY, CELL 48: 789 (1987).
(
10.1016/0092-8674(87)90076-6
) / CELL (1987) -
BURGERING, BMT, INSULIN STIMULATION OF GENE-EXPRESSION MEDIATED BY P21RAS ACTIVATION, EMBO JOURNAL 10: 1103 (1991).
(
10.1002/j.1460-2075.1991.tb08050.x
) / EMBO JOURNAL (1991) - DECLUE, J.E., SUPPRESSION OF SRC TRANSFORMATION BY OVEREXPRESSION OF FULL-LENGTH GTPASE-ACTIVATING PROTEIN (GAP) OR OF THE GAP-C TERMINUS, MOLECULAR AND CELLULAR BIOLOGY 11: 2819 (1991). / MOLECULAR AND CELLULAR BIOLOGY (1991)
- DER, C. J., ONCOGENE 3: 105 (1988). / ONCOGENE (1988)
-
DOWNWARD, J, STIMULATION OF P21RAS UPON T-CELL ACTIVATION, NATURE 346: 719 (1990).
(
10.1038/346719a0
) / NATURE (1990) - DOWNWARD, J, IDENTIFICATION OF A NUCLEOTIDE EXCHANGE-PROMOTING ACTIVITY FOR P21RAS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 87: 5998 (1990). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1990)
-
FURTH, M.E., MONOCLONAL-ANTIBODIES TO THE P21 PRODUCTS OF THE TRANSFORMING GENE OF HARVEY MURINE SARCOMA-VIRUS AND OF THE CELLULAR RAS GENE FAMILY, JOURNAL OF VIROLOGY 43: 294 (1982).
(
10.1128/jvi.43.1.294-304.1982
) / JOURNAL OF VIROLOGY (1982) -
GIBBS, J.B., MODULATION OF GUANINE-NUCLEOTIDES BOUND TO RAS IN NIH3T3 CELLS BY ONCOGENES, GROWTH-FACTORS, AND THE GTPASE ACTIVATING PROTEIN (GAP), JOURNAL OF BIOLOGICAL CHEMISTRY 265: 20437 (1990).
(
10.1016/S0021-9258(17)30523-9
) / JOURNAL OF BIOLOGICAL CHEMISTRY (1990) - HOSHINO, M, CHARACTERIZATION OF A FACTOR THAT STIMULATES HYDROLYSIS OF GTP BOUND TO RAS GENE PRODUCT-P21 (GTPASE-ACTIVATING PROTEIN) AND CORRELATION OF ITS ACTIVITY TO CELL-DENSITY, MOLECULAR AND CELLULAR BIOLOGY 8: 4169 (1988). / MOLECULAR AND CELLULAR BIOLOGY (1988)
- HUANG, Y.K., PURIFICATION OF A FACTOR CAPABLE OF STIMULATING THE GUANINE-NUCLEOTIDE EXCHANGE-REACTION OF RAS PROTEINS AND ITS EFFECT ON RAS-RELATED SMALL MOLECULAR MASS G-PROTEINS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 87: 8008 (1990). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1990)
- JONES, S, THE CDC25 PROTEIN OF SACCHAROMYCES-CEREVISIAE PROMOTES EXCHANGE OF GUANINE-NUCLEOTIDES BOUND TO RAS, MOLECULAR AND CELLULAR BIOLOGY 11: 2641 (1991). / MOLECULAR AND CELLULAR BIOLOGY (1991)
-
KAPLAN, D.R., PDGF BETA-RECEPTOR STIMULATES TYROSINE PHOSPHORYLATION OF GAP AND ASSOCIATION OF GAP WITH A SIGNALING COMPLEX, CELL 61: 125 (1990).
(
10.1016/0092-8674(90)90220-9
) / CELL (1990) - LACAL, J.C., INVOLVEMENT OF FUNCTIONAL PROTEIN-KINASE-C IN THE MITOGENIC RESPONSE TO THE H-RAS ONCOGENE PRODUCT, MOLECULAR AND CELLULAR BIOLOGY 7: 4146 (1987). / MOLECULAR AND CELLULAR BIOLOGY (1987)
-
LOWY, D.R., REGULATION OF P21RAS ACTIVITY, TRENDS IN GENETICS 7: 346 (1991).
(
10.1016/0168-9525(91)90209-9
) / TRENDS IN GENETICS (1991) 10.1016/0092-8674(90)90150-D
10.1038/342711a0
- MORAN, M.F., PROTEIN-TYROSINE KINASES REGULATE THE PHOSPHORYLATION, PROTEIN INTERACTIONS, SUBCELLULAR-DISTRIBUTION, AND ACTIVITY OF P21RAS GTPASE-ACTIVATING PROTEIN, MOLECULAR AND CELLULAR BIOLOGY 11: 1804 (1991). / MOLECULAR AND CELLULAR BIOLOGY (1991)
- MORRIS, JDH, SCRAPE-LOADING OF SWISS 3T3 CELLS WITH RAS PROTEIN RAPIDLY ACTIVATES PROTEIN KINASE-C IN THE ABSENCE OF PHOSPHOINOSITIDE HYDROLYSIS, ONCOGENE 4: 27 (1989). / ONCOGENE (1989)
-
MULCAHY, L.S., REQUIREMENT FOR RAS PROTO-ONCOGENE FUNCTION DURING SERUM-STIMULATED GROWTH OF NIH-3T3-CELLS, NATURE 313: 241 (1985).
(
10.1038/313241a0
) / NATURE (1985) - NORI, M, INHIBITION OF V-SRC-INDUCED TRANSFORMATION BY A GTPASE-ACTIVATING PROTEIN, MOLECULAR AND CELLULAR BIOLOGY 11: 2812 (1991). / MOLECULAR AND CELLULAR BIOLOGY (1991)
- PAPAGEORGE A.G. unpublished data.
- PATEL, G, ALTERNATE MECHANISMS OF RAS ACTIVATION ARE COMPLEMENTARY AND FAVOR AND FORMATION OF RAS-GTP, ONCOGENE 7: 283 (1992). / ONCOGENE (1992)
10.1126/science.3547648
- SATOH, T, PLATELET-DERIVED GROWTH-FACTOR STIMULATES FORMATION OF ACTIVE P21RAS.GTP COMPLEX IN SWISS MOUSE 3T3-CELLS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 87: 5993 (1990). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1990)
- SATOH, T, ACCUMULATION OF P21RAS.GTP IN RESPONSE TO STIMULATION WITH EPIDERMAL GROWTH-FACTOR AND ONCOGENE PRODUCTS WITH TYROSINE KINASE-ACTIVITY, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 87: 7926 (1990). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1990)
- SIGAL, I.S., MUTANT RAS-ENCODED PROTEINS WITH ALTERED NUCLEOTIDE BINDING EXERT DOMINANT BIOLOGICAL EFFECTS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 83: 952 (1986). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1986)
-
SMITH, M.R., REQUIREMENT FOR C-RAS PROTEINS DURING VIRAL ONCOGENE TRANSFORMATION, NATURE 320: 540 (1986).
(
10.1038/320540a0
) / NATURE (1986) 10.1126/science.2821624
10.1126/science.2181667
10.1016/0092-8674(90)90149-9
10.1038/346754a0
Dates
Type | When |
---|---|
Created | 18 years, 10 months ago (Oct. 5, 2006, 7:03 p.m.) |
Deposited | 1 year, 7 months ago (Jan. 10, 2024, 11:08 p.m.) |
Indexed | 1 year, 7 months ago (Jan. 15, 2024, 7 a.m.) |
Issued | 33 years ago (July 31, 1992) |
Published | 33 years ago (July 31, 1992) |
Published Print | 33 years ago (July 31, 1992) |
@article{Zhang_1992, title={Mechanistic Aspects of Signaling Through Ras in NIH 3T3 Cells}, volume={257}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1496380}, DOI={10.1126/science.1496380}, number={5070}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Zhang, Ke and Papageorge, Alex G. and Lowy, Douglas R.}, year={1992}, month=jul, pages={671–674} }