Raf kinase inhibitory protein reduces bradykinin receptor desensitization

J Neurochem. 2022 Jul;162(2):156-165. doi: 10.1111/jnc.15614. Epub 2022 May 8.


Inflammatory hyperalgesia represents a nociceptive phenotype that can become persistent in nature through dynamic protein modifications. However, a large gap in knowledge exists concerning how the integration of intracellular signaling molecules coordinates a persistent inflammatory phenotype. Herein, we demonstrate that Raf Kinase Anchoring Protein (RKIP) interrupts a vital canonical desensitization pathway to maintain bradykinin (BK) receptor activation in primary afferent neurons. Biochemical analyses of primary neuronal cultures indicate bradykinin-stimulated PKC phosphorylation of RKIP at Ser153. Furthermore, BK exposure increases G-protein Receptor Kinase 2 (GRK2) binding to RKIP, inhibiting pharmacological desensitization of the BK receptor. Additional studies found that molecular RKIP down-regulation increases BK receptor desensitization in real-time imaging of primary afferent neurons, identifying a key pathway integrator in the desensitization process that controls multiple GRK2-sensitive G-protein coupled receptors. Therefore, RKIP serves as an integral scaffolding protein that inhibits BK receptor desensitization.

Keywords: GRK2; PKC; RKIP; bradykinin; calcium.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bradykinin* / pharmacology
  • Phosphorylation
  • Receptors, Bradykinin*
  • Signal Transduction
  • Transcription Factors
  • raf Kinases


  • Receptors, Bradykinin
  • Transcription Factors
  • raf Kinases
  • Bradykinin