Journal
EXPERIMENTAL CELL RESEARCH
Volume 319, Issue 9, Pages 1289-1297Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2012.12.015
Keywords
Angiogenesis; Rho GTPase; Guanine exchange factor; GEF
Categories
Funding
- Deutsche Forschungsgemeinschaft (SFB/TR23: Integrated Research Training Group)
- project Z5 [GRK 880/3, KR1887/5-1]
- Studienstiftung des deutschen Volkes
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The angiogenic cascade is a multi-step process essential for embryogenesis and other physiological and pathological processes. Rho family GTPases are binary molecular switches and serve as master regulators of various basic cellular processes. Rho GTPases are known to exert important functions in angiogenesis and vascular physiology. These functions demand a tight and context-specific control of cellular processes requiring superordinate control by a multitude of guanine nucleotide exchange factors (GEFs). GEFs display various features enabling them to fine-tune the actions of Rho GTPases in the vasculature: (1) GEFs regulate specific steps of the angiogenic cascade; (2) GEFs show a spatio-temporally specific expression pattern; (3) GEFs differentially regulate endothelial function depending on their subcellular location; (4) GEFs mediate crosstalk between complex signaling cascades and (5) GEFs themselves are regulated by another layer of interacting proteins. The aim of this review is to provide an overview about the role of GEFs in regulating angiogenesis and vascular function and to point out current limitations as well as clinical perspectives. (C) 2012 Elsevier Inc. All rights reserved.
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