UMMS Affiliation

Program in Molecular Medicine

Publication Date


Document Type



Amino Acids, Peptides, and Proteins | Biochemistry | Cell Biology | Cells | Enzymes and Coenzymes | Molecular Biology | Nucleic Acids, Nucleotides, and Nucleosides


Detailed structural, biochemical, cell biological, and genetic studies of any gene/protein are required to develop models of its actions in cells. Studying a protein family in the aggregate yields additional information, as one can include analyses of their coevolution, acquisition or loss of functionalities, structural pliability, and the emergence of shared or variations in molecular mechanisms. An even richer understanding of cell biology can be achieved through evaluating functionally linked protein families. In this review, we summarize current knowledge of three protein families: the ARF GTPases, the guanine nucleotide exchange factors (ARF GEFs) that activate them, and the GTPase-activating proteins (ARF GAPs) that have the ability to both propagate and terminate signaling. However, despite decades of scrutiny, our understanding of how these essential proteins function in cells remains fragmentary. We believe that the inherent complexity of ARF signaling and its regulation by GEFs and GAPs will require the concerted effort of many laboratories working together, ideally within a consortium to optimally pool information and resources. The collaborative study of these three functionally connected families ( > /=70 mammalian genes) will yield transformative insights into regulation of cell signaling.


cell biology, protein families, ARF GTPases, ARF GEFs, ARF GAPs, cell signaling

Rights and Permissions

© 2019 Sztul et al. Publisher PDF posted as allowed by the publisher's author rights policy at This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (

DOI of Published Version



Mol Biol Cell. 2019 May 15;30(11):1249-1271. doi: 10.1091/mbc.E18-12-0820. Link to article on publisher's site

Journal/Book/Conference Title

Molecular biology of the cell

Related Resources

Link to Article in PubMed

PubMed ID


Creative Commons License

Creative Commons Attribution-Noncommercial-Share Alike 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License.