Dock4 forms a complex with SH3YL1 and regulates cancer cell migration

Cell Signal. 2014 May;26(5):1082-8. doi: 10.1016/j.cellsig.2014.01.027. Epub 2014 Feb 5.

Abstract

Dock4 is a member of the Dock180 family of proteins that mediates cancer cell migration through activation of Rac. However, the regulatory mechanism of Dock4 remains unclear. In this study, we show that the C-terminal proline-rich region of Dock4 is essential for the Dock4 mediated promotion of cell migration in MDA-MB-231 breast cancer cells. We found that a phosphoinositide-binding protein SH3YL1 interacted with the C-terminal proline-rich region of Dock4. Interaction of SH3YL1 with Dock4 promoted Dock4-mediated Rac1 activation and cell migration. Mutations in the phosphoinositide-binding domain disrupted the ability of SH3YL1 to promote Dock4-mediated cell migration. In addition, depletion of SH3YL1 in MDA-MB-231 cells suppressed cell migration. Taken together, these results provide evidence for a novel and functionally important interaction between Dock4 and SH3YL1 to promote cancer cell migration by regulating Rac1 activity.

Keywords: Cell migration; Dock4; GEF; Rac1; Rho family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • GTPase-Activating Proteins / chemistry
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism*
  • HEK293 Cells
  • Humans
  • Mice
  • Mutation
  • Protein Binding
  • Protein Structure, Tertiary
  • rac1 GTP-Binding Protein / metabolism

Substances

  • Carrier Proteins
  • Dock4 protein, mouse
  • GTPase-Activating Proteins
  • SH3YL1 protein, human
  • rac1 GTP-Binding Protein