The cytohesin coiled-coil domain interacts with threonine 276 to control membrane association

Kevin G. Hiester, Lorraine C. Santy

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere82084
JournalPloS one
Volume8
Issue number11
DOIs
StatePublished - Nov 26 2013

Fingerprint

Threonine
threonine
Association reactions
Membranes
cell movement
Phosphorylation
phosphorylation
proteins
Cell Movement
Proteins
guanosinetriphosphatase
aspartic acid
Monomeric GTP-Binding Proteins
Cell Shape
Aspartic Acid
Conformations
mutation
Chemical activation
Cells
Mutation

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

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The cytohesin coiled-coil domain interacts with threonine 276 to control membrane association. / Hiester, Kevin G.; Santy, Lorraine C.

In: PloS one, Vol. 8, No. 11, e82084, 26.11.2013.

Research output: Contribution to journalArticle

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