Whether your passion is to understand and reverse disease processes or “simply” a better understanding of how cells work, anyone wishing to understand cell regulation today must have a detailed and accurate understanding of regulatory GTPase mechanisms and their application to specific pathways. This is becoming increasingly difficult as the details of signaling by members of different families of GTPases and their regulators expand. But this is all the more reason to continually ask, which aspects of GTPase signaling are distinct to a GTPase or its subfamily and which are conserved throughout the superfamily? We each have slightly different views of the key aspects of GTPase signaling that are derived from the main GTPases studied in our own labs; e.g., translocation onto a membrane is an essential and integral aspect of Arf activation but not of other GTPases. However, one aspect of GTPase signaling that I had come to believe to be widespread and of general importance is not universally accepted. In fact, through my conversations at the recent FASEB summer research conference on “Arf Family GTPases” and reading of the literature in a graduate tutorial class, I realize that is not known or accepted by the majority of researchers. The question is the role of GTPase activating proteins (GAPs) in signaling. Are they “pure” terminators of signaling or do they serve effector functions?

An editorial relating to this article can be found at:

http://www.landesbioscience.com/journals/cellularlogistics/article/15738/