"Inside-out" signal transduction inhibited by isolated integrin cytoplasmic domains

J Biol Chem. 1994 Jul 15;269(28):18307-10.


The affinities of integrin alpha beta heterodimers for extracellular ligands are important regulators of cell adhesion. Intracellular signals provoke changes in the integrin extracellular domain resulting in "activation," as manifested by an increase in affinity. Interactions of integrin cytoplasmic domains with intracellular elements may mediate this "inside-out signaling." Here we report that overexpression of chimeras of the cytoplasmic domain of integrin beta 3 or beta 1 subunits, joined to the extracellular and transmembrane domains of the Tac subunit of the interleukin-2 receptor, reduced integrin affinity. In contrast, chimeras containing the cytoplasmic domain of alpha 5 or alpha IIb or of beta 3 bearing a mutation that disrupts inside-out signaling lacked inhibitory activity. These data suggest that limiting quantities of intracellular factors bind to integrin beta 3 and beta 1 cytoplasmic domains to modulate ligand binding affinity. Structural mimics of these domains may provide a novel means to alter cell adhesion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • CHO Cells
  • Cricetinae
  • Cytoplasm / physiology
  • DNA Primers
  • Flow Cytometry
  • Integrins / biosynthesis
  • Integrins / physiology*
  • Kinetics
  • Macromolecular Substances
  • Molecular Sequence Data
  • Mutagenesis
  • Polymerase Chain Reaction
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Transfection


  • DNA Primers
  • Integrins
  • Macromolecular Substances
  • Recombinant Fusion Proteins