On the mitogenic properties of Rap1b: cAMP-induced G 1 /S entry requires activated and phosphorylated Rap1b
- 16 April 2002
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 99 (8), 5418-5423
- https://doi.org/10.1073/pnas.082122499
Abstract
We have shown that the small GTPase Rap1b, a protein known to antagonize the mitogenic and transforming activity of Ras, is endowed with both mitogenic and tumorigenic properties. Rap1b can be activated by cAMP, an intracellular message known to either stimulate or inhibit cell proliferation. The oncogenic property of Rap1b was revealed in a model system in which cAMP stimulates cell proliferation and was linked to Rap's ability to promote S phase entry. We have now tested the significance of the mitogenic action of Rap1b in a physiologically relevant model, the differentiated thyroid follicular cells, a system that requires thyroid-stimulating hormone (TSH), acting via cAMP, to mediate a full mitogenic response. Here we report that cAMP-dependent hormonal stimulation of DNA synthesis requires Rap1b in a manner dependent on its phosphorylation by protein kinase A.This publication has 55 references indexed in Scilit:
- Rap1 signalling: adhering to new modelsNature Reviews Molecular Cell Biology, 2001
- Cyclic AMP activates RasOncogene, 2000
- Activation of Mitogen-activated Protein Kinase by the A2A-adenosine Receptor via a rap1-dependent and via a p21 -dependent PathwayOnline Journal of Public Health Informatics, 1999
- Biochemical characterization of C3G: an exchange factor that discriminates between Rap1 and Rap2 and is not inhibited by Rap1A(S17N)Oncogene, 1997
- Insulin, growth factors, and cAMP: Antagonism in the signal transduction pathwaysTrends in Endocrinology & Metabolism, 1996
- rap1 p21 regulates the interaction of ras p21 with RGL, a new effector protein of ras p21FEBS Letters, 1995
- The 2.2 Å crystal structure of the Ras-binding domain of the serine/threonine kinase c-Raf1 in complex with RaplA and a GTP analogueNature, 1995
- Structures and functions of the Krev-1 transformation suppressor gene and its relativesBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1993
- Inhibition of GTPase Activating Protein Stimulation of Ras-p21 GTPase by the K rev -1 Gene ProductScience, 1990
- The cyclic AMP-mediated stimulation of cell proliferationTrends in Biochemical Sciences, 1989