Journal
CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY
Volume 53, Issue 2, Pages 130-156Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10409238.2018.1431605
Keywords
Effectors; GAPs; GEFs; protein family; RAS; scaffold proteins; signal transduction
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Funding
- Research committee of the Medical Faculty of the Heinrich-Heine University Dusseldorf (FoKo) [9772617]
- German Research Foundation (Deutsche Forschungsgemeinschaft or DFG) through the Collaborative Research Center [SFB 974]
- German Federal Ministry of Education and Research (BMBF) - German Network of RASopathy Research (GeNeRARe)
- European Network on Noonan Syndrome and Related Disorders (NSEuroNet)
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Among the signaling molecules indirectly linked to many different cell surface receptors, RAS proteins essentially respond to a diverse range of extracellular cues. They control activities of multiple signaling pathways and consequently a wide array of cellular processes, including survival, growth, adhesion, migration, and differentiation. Any dysregulation of these pathway leads, thus, to cancer, developmental disorders, metabolic, and cardiovascular diseases. The biochemistry of RAS family proteins has become multifaceted since the discovery of the first members, more than 40 years ago. Substantial knowledge has been attained about molecular mechanisms underlying post-translational modification, membrane localization, regulation, and signal transduction through diverse effector molecules. However, the increasing complexity of the underlying signaling mechanisms is considerable, in part due to multiple effector pathways, crosstalks between them and eventually feedback mechanisms. Here, we take a broad view of regulatory and signaling networks of all RAS family proteins that extends beyond RAS paralogs. As described in this review, a lot is known but a lot has to be discovered yet.
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