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G-Protein-Coupled Receptors Signaling to MAPK/Erk

© Cell Signaling Technology. All Rights Reserved.
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Pathway Description:

G protein-coupled receptors (GPCRs) are activated by a wide variety of external stimuli. Upon receptor activation, the G protein exchanges GDP for GTP, causing the dissociation of the GTP-bound α and β/γ subunits and triggering diverse signaling cascades. Receptors coupled to different heterotrimeric G protein subtypes can utilize different scaffolds to activate the small G protein/ MAPK cascade, employing at least three different classes of Tyr kinases. Src family kinases are recruited following activation of PI3Kγ by β/γ subunits. They are also recruited by receptor internalization, crossactivation of receptor Tyr kinases, or by signaling through an integrin scaffold involving Pyk2 and/or FAK. GPCRs can also employ PLCβ to mediate activation of PKC and CaMKII, which can have either stimulatory or inhibitory consequences for the downstream MAPK pathway.

Selected Reviews:

We would like to thank Prof. John Blenis, Harvard Medical School, Boston, MA, for reviewing this diagram.

created October 2002

revised October 2012

  • KinaseKinase
  • PhosphatasePhosphatase
  • Transcription FactorTranscription Factor
  • CaspaseCaspase
  • ReceptorReceptor
  • EnzymeEnzyme
  • pro-apoptoticpro-apoptotic
  • pro-survivalpro-survival
  • GTPaseGTPase
  • G-proteinG-protein
  • AcetylaseAcetylase
  • DeacetylaseDeacetylase
  • Ribosomal subunitRibosomal subunit
  • Direct Stimulatory ModificationDirect Stimulatory Modification
  • Direct Inhibitory ModificationDirect Inhibitory Modification
  • Multistep Stimulatory ModificationMultistep Stimulatory Modification
  • Multistep Inhibitory ModificationMultistep Inhibitory Modification
  • Tentative Stimulatory ModificationTentative Stimulatory Modification
  • Tentative Inhibitory ModificationTentative Inhibitory Modification
  • Separation of Subunits or Cleavage ProductsSeparation of Subunits or Cleavage Products
  • Joining of SubunitsJoining of Subunits
  • TranslocationTranslocation
  • Transcriptional Stimulatory ModificationTranscriptional Stimulatory Modification
  • Transcriptional Inhibitory ModificationTranscriptional Inhibitory Modification