Abstract
GTPases (GTP hydrolases, GTP-binding proteins) are enzymes that direct various cellular functions, including signal transduction, protein biosynthesis, cell division, and transport of vesicles. They are molecular switches that cycle between two conformational states (Fig. 1): the inactive guanosine-5′-diphosphate (GDP)-bound state and the active guanosine-5′-triphosphate (GTP)-bound-state. In the GTP-bound ‘on’ state GTPases bind effector proteins and generate cellular responses, until GTP hydrolysis returns the switch to the ‘off’ state. GTP binding and hydrolysis occur in the highly conserved G domain. GTPases are characterized by low intrinsic GDP–GTP exchange and GTP hydrolysis rates; thus, both processes need to be controlled by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) in order for the molecular switch to function at physiologically relevant rates. With few exceptions, GTPases are grouped into two main superfamilies: heterotrimeric G proteins and small GTPases. In this chapter, we will summarize the current state of knowledge about the role of these proteins in the regulation of platelet functional responses, with a particular focus on the tight functional interrelationship between the most well-studied members of the two families.
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Acknowledgement
This work was supported by grants from the National Heart, Lung, and Blood Institute of the National Institutes of Health (W.B.) and the Program for Young Researchers “Rita Levi Montalcini” (L.S.).
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Stefanini, L., Lee, R.H., Bergmeier, W. (2017). GTPases. In: Gresele, P., Kleiman, N., Lopez, J., Page, C. (eds) Platelets in Thrombotic and Non-Thrombotic Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-47462-5_20
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