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Tethered Agonism: A Common Activation Mechanism of Adhesion GPCRs

  • Ines Liebscher
  • Torsten Schöneberg
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 234)

Graphical Abstract

Adhesion GPCRs harbor a tethered agonist sequence (reproduced from [24])

Abstract

As the past years have seen a magnificent increase in knowledge on adhesion GPCR (aGPCR) signal transduction, the time had come to fill the gap on how these receptors can be activated. Based on experimental observations that deletion of the ectodomain can induce signaling, the idea arose that aGPCRs, just like other atypical GPCRs, may harbor a tethered agonist sequence. In this chapter, we describe the recent findings and characteristics of this agonist, called the Stachel sequence, and discuss potential mechanisms that cause liberation of this encrypted sequence. Further, we provide perspectives for application of Stachel-derived synthetic peptides in future studies of aGPCR function.

Keywords

Adhesion GPCR Signal transduction Tethered agonism Activation mechanism Peptide agonist 

Notes

Acknowledgments

This work was supported by the Deutsche Forschungsgemeinschaft (FOR2149, Projects 4 & 5) and the BMBF (IFB AdipositasDiseases Leipzig ADI-K767).

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Copyright information

© Springer International Publishing AG 2016

Authors and Affiliations

  1. 1.Medical FacultyInstitute of Biochemistry, University LeipzigLeipzigGermany

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