Arf GTPases and their GEFs and GAPS: Concepts and challenges

Elizabeth Sztul, Pei Wen Chen, James E. Casanova, Jacqueline Cherfils, Joel B. Dacks, David G. Lambright, Fang Jen S. Lee, Paul A. Randazzo, Lorraine C. Santy, Annette Schürmann, Ilka Wilhelmi, Marielle E. Yohe, Richard A. Kahn

Research output: Contribution to journalReview articlepeer-review

28 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1249-1271
Number of pages23
JournalMolecular biology of the cell
Volume30
Issue number11
DOIs
StatePublished - 2019

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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