Controlling protein association and subcellular localization with a synthetic ligand that induces heterodimerization of proteins

Proc Natl Acad Sci U S A. 1996 May 14;93(10):4604-7. doi: 10.1073/pnas.93.10.4604.

Abstract

Extracellular growth and differentiation factors induce changes in gene expression in the nucleus by initiating a series of protein associations that alter the subcellular localization of intracellular signaling proteins. Initial events involve receptor homo- or heterodimerization and subsequent recruitment of cytosolic signaling proteins to the inner leaflet of the plasma membrane. Intermediate events involve the translocation of proteins into the nucleus. Late events involve the recruitment of transcriptional activators to the vicinity of specific genes in the nucleus, resulting in increased gene transcription. The ability to induce signals at each of these three phases of signaling pathways is illustrated by the use of a heterodimeric chemical inducer of dimerization that causes a proximal relationship between two different target proteins.

Publication types

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

MeSH terms

  • Animals
  • Cell Line
  • Cell Membrane / metabolism
  • Cell Nucleus / metabolism
  • Gene Expression
  • Genes, Reporter
  • Humans
  • Ligands
  • Mice
  • Microscopy, Fluorescence
  • Protein Conformation
  • Protein Sorting Signals / chemistry
  • Protein Sorting Signals / genetics
  • Protein Sorting Signals / metabolism
  • Proteins / chemistry*
  • Proteins / genetics
  • Proteins / metabolism*
  • Subcellular Fractions / metabolism
  • Transcriptional Activation

Substances

  • Ligands
  • Protein Sorting Signals
  • Proteins