The Cytohesin Coiled-Coil Domain Interacts with Threonine 276 to Control Membrane Association

Cell migration is regulated by a number of small GTPases, including members of the Arf family. Cytohesins, a family of Arf-activating proteins, have been extensively implicated in the regulation of Arfs during migration and cell shape change. Membrane association of both the Arf and its activating protein is a prerequisite for Arf activation. Therefore regulating the extent of cytohesin membrane association is a mechanism for controlling the initiation of cell movement. We have discovered a novel intramolecular interaction that controls the association of cytohesins with membranes. The presence of the coiled-coil domain reduces the association of cytohesin 2 with membranes. We demonstrate that this domain interacts with more C-terminal regions of the protein. This interaction is independent of another previously identified autoinhibitory conformation. A threonine residue (T276) in the cytohesin 2 PH domain is a target for phosphorylation by Akt. Mutation of this threonine to aspartic acid, to mimic phosphorylation, disrupts the binding of the coiled-coil domain to c-terminal regions and promotes membrane association of cytohesin 2. The presence of a second autoinhibitory interaction in the cytohesins suggests that these proteins can act a signal integrators that stimulate migration only after receive multiple pro-migratory signals.

• Publication year

  2013

• Venue

  PLoS ONE

• Publication date

  2013-11-26

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.pone.0082084PMID 24303080PMCID 3841123
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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