The discovery of signal transduction by G proteins: a personal account and an overview of the initial findings and contributions that led to our present understanding

Biochim Biophys Acta. 2007 Apr;1768(4):756-71. doi: 10.1016/j.bbamem.2006.09.027. Epub 2006 Oct 4.


The realization that there existed a G-protein coupled signal transduction mechanism developed gradually and was initially the result of an ill fated quest for uncovering the mechanism of action of insulin, followed by a refocused research in many laboratories, including mine, on how GTP acted to increase hormonal stimulation of adenylyl cyclase. Independent research into how light-activated rhodopsin triggers a response in photoreceptor cells of the retina and the attendant biochemical studies joined midway and, without the left hand knowing well what the right hand was doing, preceded classical G protein research in identifying the molecular players responsible for signal transduction by G proteins.

Publication types

  • Historical Article
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adenylyl Cyclases / drug effects
  • Adenylyl Cyclases / history
  • Adenylyl Cyclases / metabolism
  • Animals
  • Binding Sites
  • Cholera Toxin / history
  • Cholera Toxin / metabolism
  • GTP Phosphohydrolases / metabolism
  • GTP-Binding Protein alpha Subunits, Gi-Go / history
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
  • GTP-Binding Protein alpha Subunits, Gs / history
  • GTP-Binding Protein alpha Subunits, Gs / metabolism
  • Guanine Nucleotides / history
  • Guanine Nucleotides / metabolism
  • Heterotrimeric GTP-Binding Proteins / genetics
  • Heterotrimeric GTP-Binding Proteins / history*
  • Heterotrimeric GTP-Binding Proteins / metabolism
  • History, 20th Century
  • History, 21st Century
  • Pertussis Toxin / history
  • Pertussis Toxin / metabolism


  • Guanine Nucleotides
  • Cholera Toxin
  • Pertussis Toxin
  • GTP Phosphohydrolases
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • GTP-Binding Protein alpha Subunits, Gs
  • Heterotrimeric GTP-Binding Proteins
  • Adenylyl Cyclases