Inside-out, outside-in, and inside-outside-in: G protein signaling in integrin-mediated cell adhesion, spreading, and retraction

Curr Opin Cell Biol. 2012 Oct;24(5):600-6. doi: 10.1016/ Epub 2012 Sep 11.


The integrin family of cell adhesion receptors mediates bi-directional signaling: 'inside-out' signaling activates the ligand binding function of integrins and 'outside-in' signaling mediates cellular responses induced by ligand binding to integrins leading to cell spreading, retraction, migration, and proliferation. Integrin signaling requires both heterotrimeric G proteins and monomeric small G proteins. This review focuses on recent development in the roles of G proteins in integrin outside-in signaling. The finding of direct interaction between the heterotrimeric G protein subunit Gα13 and integrin β subunits reveals a new mechanism for integrin signaling, and also uncovers a crosstalk between the signaling pathways initiated by G protein-coupled receptors (GPCRs) and integrins. This crosstalk, which may be referred to as 'inside-outside-in' signaling, dynamically regulates contractility and greatly promotes integrin outside-in signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Adhesion / physiology*
  • Cell Size
  • Cell Surface Extensions / metabolism*
  • GTP-Binding Protein alpha Subunits, G12-G13 / metabolism
  • Heterotrimeric GTP-Binding Proteins / chemistry
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Humans
  • Integrins / chemistry
  • Integrins / metabolism*
  • Signal Transduction / physiology*


  • Integrins
  • GTP-Binding Protein alpha Subunits, G12-G13
  • Heterotrimeric GTP-Binding Proteins