Accumulation of p21ras.GTP in response to stimulation with epidermal growth factor and oncogene products with tyrosine kinase activity
- PMID: 2146678
- PMCID: PMC54864
- DOI: 10.1073/pnas.87.20.7926
Accumulation of p21ras.GTP in response to stimulation with epidermal growth factor and oncogene products with tyrosine kinase activity
Abstract
The ras gene product (p21) is a GTP-binding protein and has been thought to transduce signals regulating proliferation or differentiation of cells. Like other GTP-binding proteins, p21.GTP is an active conformation, which can transduce the signals downstream, whereas p21.GDP is an inactive one. Recently, we have shown that p21.GTP levels increased in cells treated with fetal bovine serum or platelet-derived growth factor to initiate DNA synthesis. In this paper, we report that epidermal growth factor can also increase the amounts of p21.GTP in the cells. Effects of epidermal growth factor and platelet-derived growth factor are not additive. In contrast, mutant [Val12]p21, which has transforming activity, responded neither to platelet-derived growth factor nor to epidermal growth factor. We also found that the ratio of p21.GTP to p21.GDP increased 3- to 4-fold in transformants carrying activated erbB-2/neu or v-src oncogenes. These results strongly suggest an important role of p21 in transduction of signals for both normal proliferation and malignant transformation through growth factor receptors with tyrosine kinase activity or related oncogene products.
Similar articles
-
Role of p21 RAS in p210 bcr-abl transformation of murine myeloid cells.Blood. 1993 Sep 15;82(6):1838-47. Blood. 1993. PMID: 7691239
-
Platelet-derived growth factor stimulates formation of active p21ras.GTP complex in Swiss mouse 3T3 cells.Proc Natl Acad Sci U S A. 1990 Aug;87(15):5993-7. doi: 10.1073/pnas.87.15.5993. Proc Natl Acad Sci U S A. 1990. PMID: 2198577 Free PMC article.
-
The E5 gene product of rhesus papillomavirus is an activator of endogenous Ras and phosphatidylinositol-3'-kinase in NIH 3T3 cells.Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):12879-84. doi: 10.1073/pnas.93.23.12879. Proc Natl Acad Sci U S A. 1996. PMID: 8917513 Free PMC article.
-
Regulation of platelet-derived growth factor signaling by activated p21Ras.Front Biosci. 1999 Jan 15;4:D72-86. doi: 10.2741/stice. Front Biosci. 1999. PMID: 9889183 Review.
-
Polypeptide growth factors: roles in normal and abnormal cell growth.Annu Rev Cell Biol. 1987;3:443-92. doi: 10.1146/annurev.cb.03.110187.002303. Annu Rev Cell Biol. 1987. PMID: 3318882 Review.
Cited by
-
K15 promoter-driven enforced expression of NKIRAS exhibits tumor suppressive activity against the development of DMBA/TPA-induced skin tumors.Sci Rep. 2021 Oct 19;11(1):20658. doi: 10.1038/s41598-021-00200-1. Sci Rep. 2021. PMID: 34667224 Free PMC article.
-
Emerging roles of PLCγ1 in endothelial biology.Sci Signal. 2021 Aug 3;14(694):eabc6612. doi: 10.1126/scisignal.abc6612. Sci Signal. 2021. PMID: 34344833 Free PMC article. Review.
-
Oncogenic Ras mutant causes the hyperactivation of NF-κB via acceleration of its transcriptional activation.Mol Oncol. 2019 Nov;13(11):2493-2510. doi: 10.1002/1878-0261.12580. Epub 2019 Oct 18. Mol Oncol. 2019. PMID: 31580526 Free PMC article.
-
Single-molecule fluorescence imaging of RalGDS on cell surfaces during signal transduction from Ras to Ral.Biophys Physicobiol. 2017 Jun 1;14:75-84. doi: 10.2142/biophysico.14.0_75. eCollection 2017. Biophys Physicobiol. 2017. PMID: 28744424 Free PMC article.
-
Cardiac Hormones Target the Ras-MEK 1/2-ERK 1/2 Kinase Cancer Signaling Pathways.Cancers (Basel). 2011 Mar 8;3(1):1182-94. doi: 10.3390/cancers3011182. Cancers (Basel). 2011. PMID: 24212659 Free PMC article.
References
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous