Journal
LIFE SCIENCES
Volume 88, Issue 15-16, Pages 645-652Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2011.01.023
Keywords
Rap1; cAMP; Epac
Funding
- National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) [R21HL088087, T32HL098039-01]
- American Heart Association (AHA), Great Rivers Affiliate [0765204B]
- The Research Institute at Nationwide Children's Hospital, Columbus, Ohio
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The Ras related GTPase Rap has been implicated in multiple cellular functions. A vital role for Rap GTPase in the cardiovasculature is emerging from recent studies. These small monomeric G proteins act as molecular switches, coupling extracellular stimulation to intracellular signaling through second messengers. This member of the Ras superfamily was once described as the transformation suppressor with the ability to ameliorate the Ras transformed phenotype: however, further studies uncovered a unique set of guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs) and effector proteins for Rap suggesting a more sophisticated role for this small GTPase. At least three different second messengers can activate Rap, namely cyclic AMP (cAMP), calcium and diacylglycerol. More recently, an investigation of Rap in the cardiovasculature has revealed multiple pathways of regulation involving Rap in this system. Two closely related isoforms of Rap1 exist, 1a and 1b. Murine genetic models exist for both and have been described. Although thought at first to be functionally redundant, these isoforms have differing roles in the cardiovasculature. The activation of Rap1a and 1b in various cell types of the cardiovasculature leads to alterations in cell attachment, migration and cell junction formation. This review will focus on the role of these Rap1 GTPases in hematopoietic, endothelial, smooth muscle, and cardiac myocyte function, and conclude with their potential role in human disease. (C) 2011 Elsevier Inc. All rights reserved.
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