GPCR-ErbB transactivation pathways and clinical implications

Cell Signal. 2021 Oct:86:110092. doi: 10.1016/j.cellsig.2021.110092. Epub 2021 Jul 22.

Abstract

Cell surface receptors including the epidermal growth factor receptor (EGFR) family and G-protein coupled receptors (GPCRs) play quintessential roles in physiology, and in diseases, including cardiovascular diseases. While downstream signaling from these individual receptor families has been well studied, the cross-talk between EGF and GPCR receptor families is still incompletely understood. Including members of both receptor families, the number of receptor and ligand combinations for unique interactions is vast, offering a frontier of pharmacologic targets to explore for preventing and treating disease. This molecular cross-talk, called receptor transactivation, is reviewed here with a focus on the cardiovascular system featuring the well-studied GPCR receptors, but also discussing less-studied receptors from both families for a broad understanding of context of expansile interactions, repertoire of cellular signaling, and disease consequences. Attention is given to cell type, level of chronicity, and disease context given that transactivation and comorbidities, including diabetes, hypertension, coronavirus infection, impact cardiovascular disease and health outcomes.

Keywords: Cardiovascular diseases; EGFR family signaling; GPCR; Transactivation.

Publication types

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

MeSH terms

  • Animals
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / pathology*
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Humans
  • Isoproterenol / chemistry
  • Isoproterenol / metabolism
  • Matrix Metalloproteinase 14 / metabolism
  • Receptors, Adrenergic, beta / metabolism
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction
  • Transcriptional Activation

Substances

  • Receptors, Adrenergic, beta
  • Receptors, G-Protein-Coupled
  • ErbB Receptors
  • Matrix Metalloproteinase 14
  • Isoproterenol