GPCR-ErbB transactivation pathways and clinical implications

Area of Science:

• Molecular biology and pharmacology
• Cardiovascular physiology and disease

Background:

• Cell surface receptors like epidermal growth factor receptor (EGFR) and G-protein coupled receptors (GPCRs) are vital in normal physiology and disease.
• Individual signaling pathways of EGFR and GPCR families are well-understood, but their cross-talk remains incompletely elucidated.
• The vast number of receptor-ligand interactions presents a significant area for pharmacological intervention.

Purpose of the Study:

• To review the molecular cross-talk, termed receptor transactivation, between EGFR and GPCR families.
• To focus on the cardiovascular system, highlighting both well-studied GPCRs and lesser-known receptors from both families.
• To provide a broad understanding of the context, signaling repertoire, and disease implications of receptor transactivation.

Main Methods:

• Literature review focusing on receptor transactivation mechanisms.
• Analysis of signaling pathways involving EGFR and GPCRs in the cardiovascular context.
• Consideration of factors influencing transactivation, including cell type, chronicity, and comorbidities.

Main Results:

• Receptor transactivation represents a complex interplay between EGFR and GPCR signaling pathways.
• This cross-talk significantly influences cardiovascular function and disease development.
• Comorbidities such as diabetes, hypertension, and viral infections can modulate these interactions and impact cardiovascular outcomes.

Conclusions:

• Receptor transactivation is a critical mechanism in cardiovascular physiology and pathology.
• Further research into these interactions, considering various biological contexts, is essential for developing novel therapeutic strategies.
• Targeting receptor transactivation pathways holds promise for managing cardiovascular diseases and associated comorbidities.