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Pleiotropic Roles of Calmodulin in the Regulation of KRas and Rac1 GTPases: Functional Diversity in Health and Disease
- Source :
- International Journal of Molecular Sciences, Vol 21, Iss 3680, p 3680 (2020), Dipòsit Digital de la UB, Universidad de Barcelona, International Journal of Molecular Sciences
- Publication Year :
- 2020
- Publisher :
- MDPI AG, 2020.
-
Abstract
- Calmodulin is a ubiquitous signalling protein that controls many biological processes due to its capacity to interact and/or regulate a large number of cellular proteins and pathways, mostly in a Ca2+-dependent manner. This complex interactome of calmodulin can have pleiotropic molecular consequences, which over the years has made it often difficult to clearly define the contribution of calmodulin in the signal output of specific pathways and overall biological response. Most relevant for this review, the ability of calmodulin to influence the spatiotemporal signalling of several small GTPases, in particular KRas and Rac1, can modulate fundamental biological outcomes such as proliferation and migration. First, direct interaction of calmodulin with these GTPases can alter their subcellular localization and activation state, induce post-translational modifications as well as their ability to interact with effectors. Second, through interaction with a set of calmodulin binding proteins (CaMBPs), calmodulin can control the capacity of several guanine nucleotide exchange factors (GEFs) to promote the switch of inactive KRas and Rac1 to an active conformation. Moreover, Rac1 is also an effector of KRas and both proteins are interconnected as highlighted by the requirement for Rac1 activation in KRas-driven tumourigenesis. In this review, we attempt to summarize the multiple layers how calmodulin can regulate KRas and Rac1 GTPases in a variety of cellular events, with biological consequences and potential for therapeutic opportunities in disease settings, such as cancer.
- Subjects :
- rac1 GTP-Binding Protein
Cellular signal transduction
Calmodulin
Carcinogenesis
RAC1
Review
GTPase
Biology
medicine.disease_cause
Interactome
Catalysis
Proto-Oncogene Proteins p21(ras)
Inorganic Chemistry
lcsh:Chemistry
calmodulin-binding proteins
medicine
Calmodulina
KRas
Animals
Humans
Physical and Theoretical Chemistry
signalling
Molecular Biology
lcsh:QH301-705.5
Spectroscopy
Effector
Organic Chemistry
Transducció de senyal cel·lular
Genetic Pleiotropy
General Medicine
Calmodulin-binding proteins
Computer Science Applications
Cell biology
lcsh:Biology (General)
lcsh:QD1-999
biology.protein
Guanine nucleotide exchange factor
KRAS
Rac1
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 16616596 and 14220067
- Volume :
- 21
- Issue :
- 3680
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....928b67ec5c8570f84c703144039815e0