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Ras and Rap1: two highly related small GTPases with distinct function
1Laboratory for Physiological Chemistry, Center for Biomedical Genetics, Utrecht University, Universiteitsweg 100, Utrecht, 3584 CG, The Netherlands.
Experimental Cell Research
|December 2, 1999
Summary
The small GTPase Rap1 antagonizes Ras, regulating cellular processes like morphology. Rap1 activation, influenced by cAMP via Epac, offers a novel signaling pathway distinct from Ras.
Area of Science:
- Molecular Biology
- Cell Signaling
Background:
- The Ras-like family of small GTPases, including Ras and Rap1, share effector domain similarities.
- While Ras function is partially understood, Rap1's role remains less defined.
- Rap1 was initially identified as a suppressor of Ras-induced cell transformation.
Purpose of the Study:
- To investigate the signaling pathways and cellular functions of the small GTPase Rap1.
- To explore the relationship between Rap1 and Ras in cellular processes.
- To elucidate novel Rap1 activation mechanisms.
Main Methods:
- Analysis of Rap1 activation in response to receptor stimulation.
- Identification of second messengers (calcium, diacylglycerol, cAMP) mediating Rap1 activation.
- Characterization of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) involved in Rap1 regulation.
Main Results:
- Rap1 is rapidly activated by diverse receptor signals.
- Epac, a cAMP-activated GEF, mediates a novel protein kinase A-independent pathway for Rap1 activation.
- Rap1 inactivation involves specific GAPs, including one interacting with Galphai.
- Evidence suggests Rap1 regulates unique cellular processes, potentially including cell morphology control.
Conclusions:
- Rap1 plays a distinct role in cellular signaling, antagonizing Ras in some contexts.
- Novel cAMP-dependent pathways, such as Epac, are critical for Rap1 activation.
- Rap1's functions extend beyond Ras antagonism, impacting cellular morphology and response to extracellular cues.