Abstract
Quiescent Swiss 3T3 cells can be induced to re-enter the cell cycle by stimulation of a variety of growth factor-dependent signal transduction cascades. We have utilised this cell system to investigate the point of convergence of mitogenic signalling by analysing the changes that distinct mitogens induce in the components of the cell cycle regulatory machinery (the G1 cyclins, cdks and their inhibitors). In the presence of insulin, activation of cAMP-dependent protein kinase caused a dramatic post-transcriptional down-regulation of p27Kip1, an increase in cyclin D3 but had little effect on cyclin D1 levels, whilst activation of protein kinase C had a more modest effect on cyclin D3 and p27Kip1 but caused a striking elevation in the expression of cyclin D1. The neuropeptide bombesin, when combined with insulin, caused increased expression of cyclin D1 and down-regulation of p27Kip1 mRNA and protein. Thus each combination of mitogenic agents had different effects on the components responsible for regulating the orderly progression of the cell cycle. This outcome is incompatible with a single route to mitogenesis and demonstrates that different mitogens remain distinct in the signalling responses they initiate, only converging at the levels of the expression of the D-type cyclins and the inhibitor p27Kip1.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mann, D., Higgins, T., Jones, N. et al. Differential control of cyclins D1 and D3 and the cdk inhibitor p27Kip1 by diverse signalling pathways in Swiss 3T3 cells. Oncogene 14, 1759–1766 (1997). https://doi.org/10.1038/sj.onc.1201134
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201134
Keywords
This article is cited by
-
Novel properties of the cyclin encoded by Human Herpesvirus 8 that facilitate exit from quiescence
Oncogene (2001)
-
p27Kip1-deficient mice exhibit accelerated growth hormone-releasing hormone (GHRH)-induced somatotrope proliferation and adenoma formation
Oncogene (2000)
-
Differential expression of the cyclin-dependent kinase inhibitor P27 in primary hepatocytes in early-mid G1 and G1/S transitions
Oncogene (1999)