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      Control of cell signaling by Arf GTPases and their regulators: Focus on links to cancer and other GTPase families

      , , ,
      Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
      Elsevier BV

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          Abstract

          The ADP-ribosylation factors (Arfs) comprise a family of regulatory GTP binding proteins. The Arfs regulate membrane trafficking and cytoskeleton remodeling, processes critical for eukaryotes and which have been the focus of most studies on Arfs. A more limited literature describes a role in signaling and in integrating several signaling pathways to bring about specific cell behaviors. Here, we will highlight work describing function of Arf1, Arf6 and several effectors and regulators of Arfs in signaling.

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          Endocytosis and signalling: intertwining molecular networks.

          Cell signalling and endocytic membrane trafficking have traditionally been viewed as distinct processes. Although our present understanding is incomplete and there are still great controversies, it is now recognized that these processes are intimately and bidirectionally linked in animal cells. Indeed, many recent examples illustrate how endocytosis regulates receptor signalling (including signalling from receptor tyrosine kinases and G protein-coupled receptors) and, conversely, how signalling regulates the endocytic pathway. The mechanistic and functional principles that underlie the relationship between signalling and endocytosis in cell biology are becoming increasingly evident across many systems.
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            Rho GTPases in cell biology.

            Rho GTPases are molecular switches that control a wide variety of signal transduction pathways in all eukaryotic cells. They are known principally for their pivotal role in regulating the actin cytoskeleton, but their ability to influence cell polarity, microtubule dynamics, membrane transport pathways and transcription factor activity is probably just as significant. Underlying this biological complexity is a simple biochemical idea, namely that by switching on a single GTPase, several distinct signalling pathways can be coordinately activated. With spatial and temporal activation of multiple switches factored in, it is not surprising to find Rho GTPases having such a prominent role in eukaryotic cell biology.
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              Scaffold proteins: hubs for controlling the flow of cellular information.

              The spatial and temporal organization of molecules within a cell is critical for coordinating the many distinct activities carried out by the cell. In an increasing number of biological signaling processes, scaffold proteins have been found to play a central role in physically assembling the relevant molecular components. Although most scaffolds use a simple tethering mechanism to increase the efficiency of interaction between individual partner molecules, these proteins can also exert complex allosteric control over their partners and are themselves the target of regulation. Scaffold proteins offer a simple, flexible strategy for regulating selectivity in pathways, shaping output behaviors, and achieving new responses from preexisting signaling components. As a result, scaffold proteins have been exploited by evolution, pathogens, and cellular engineers to reshape cellular behavior.
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                Author and article information

                Journal
                Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
                Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
                Elsevier BV
                01674889
                February 2022
                February 2022
                : 1869
                : 2
                : 119171
                Article
                10.1016/j.bbamcr.2021.119171
                34774605
                25a1f342-16bb-4757-b9f6-6b3e9cf4019e
                © 2022

                https://www.elsevier.com/tdm/userlicense/1.0/

                http://www.elsevier.com/open-access/userlicense/1.0/

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