Related Experiment Videos
TSH and cAMP do not signal mitogenesis through Ras activation
A Van Keymeulen1, P P Roger, J E Dumont
1Institute of Interdisciplinary Research (IRIBHN), Université Libre de Bruxelles, Campus Erasme, 808 Route de Lennik, Brussels, B-1070, Belgium. avkeymeu@ulb.ac.be
Biochemical and Biophysical Research Communications
|June 30, 2000
Summary
Ras activation is crucial for cell growth, but not for TSH/cAMP-stimulated thyrocyte proliferation. This study shows Ras-GTP levels do not increase during TSH/cAMP-induced G1 phase progression in dog thyrocytes.
Area of Science:
- Cell biology
- Molecular signaling
- Endocrinology
Background:
- Ras signaling pathways are widely recognized as critical regulators of cell cycle progression and mitogenesis.
- Receptor tyrosine kinases and serpentine receptors typically activate Ras, promoting G1 phase entry.
Purpose of the Study:
- To investigate the role of Ras activation in mitogenesis induced by various stimuli in primary dog thyrocytes.
- To determine if Ras activation is a necessary signaling event for TSH/cAMP-mediated G1 phase progression.
Main Methods:
- Primary dog thyrocytes were utilized as a physiologically relevant model system.
- Levels of GTP-bound Ras (active Ras) were measured in response to various mitogenic and comitogenic stimuli.
- Stimuli included epidermal growth factor (EGF), hepatocyte growth factor (HGF), phorbol esters, insulin, carbachol, thyroid-stimulating hormone (TSH), and forskolin.
Main Results:
- Accumulation of GTP-Ras was observed as an early convergence point for EGF, HGF, phorbol esters, insulin, and carbachol.
- Basal GTP-Ras levels were slightly decreased by TSH and forskolin.
- TSH and forskolin did not lead to an increase in GTP-Ras during the cAMP-dependent progression into G1 phase.
Conclusions:
- Ras activation is essential for mitogenesis induced by receptor tyrosine kinases and serpentine receptors in dog thyrocytes.
- Ras activation is not required for TSH/cAMP-stimulated G1 phase progression and mitogenesis in these cells.
- The TSH/cAMP signaling pathway leading to thyrocyte proliferation operates independently of Ras activation.