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Transactivation of receptor tyrosine kinases by purinergic P2Y and adenosine receptors

F G Vázquez-Cuevas1, M Reyna-Jeldes2,3,4, E Velázquez-Miranda5

  • 1Departamento de Neurobiología Celular Y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Boulevard Juriquilla # 3001, Juriquilla, Querétaro, 76230, México. fvazquez@comunidad.unam.mx.

Purinergic Signalling
|December 18, 2022
PubMed

Insights

G-protein-coupled receptors (GPCRs) can activate receptor tyrosine kinases (RTKs) through transactivation. This review details how purinergic receptors, a type of GPCR, transactivate RTKs, impacting cell physiology and disease.

Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Pharmacology

Background:

  • G-protein-coupled receptors (GPCRs) classically activate their own signaling pathways.
  • Receptor tyrosine kinases (RTKs) are key mediators of growth factor signaling.
  • RTK transactivation by GPCRs represents a significant crosstalk mechanism in intracellular signaling.

Purpose of the Study:

  • To systematically review experimental evidence of purinergic receptor-mediated RTK transactivation.
  • To explore the role of this crosstalk in various tissues and pathophysiological conditions.
  • To highlight the significance of purinergic receptor-RTK interactions for understanding GPCR signaling complexity.

Main Methods:

  • Systematic review of existing experimental data.
  • Analysis of studies investigating purinergic receptors (P2Y and adenosine) and their interaction with RTKs.
  • Focus on evidence from multiple tissues and pathophysiological contexts.

Main Results:

  • Purinergic receptors, a class A GPCR subgroup, demonstrate the ability to transactivate RTKs.
  • This transactivation modulates cellular physiology across diverse tissues and conditions.
  • Crosstalk between purinergic receptors and epidermal growth factor receptor (EGFR) is a notable redundant pathway in pathophysiology.

Conclusions:

  • Purinergic receptor-mediated RTK transactivation is a crucial mechanism linking GPCRs to cell proliferation and differentiation.
  • Understanding these pathways enhances knowledge of GPCR signal transduction complexity.
  • Targeting purinergic receptor-regulated pathways offers potential for pharmacologic interventions in disease.
Keywords:
Adenosine receptorsEGFRGPCRP2Y receptorPurinergic receptorsRTKTransactivation

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