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ERK Activation Pathways Downstream of GPCRs.

Ruchi Jain1, Uchenna Watson2, Lakshmi Vasudevan3

  • 1Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India.

International Review of Cell and Molecular Biology
|April 28, 2018
PubMed
Summary

G protein-coupled receptors (GPCRs) can activate mitogen-activated protein kinase (MAPK) pathways, influencing cell fate. This review details GPCR-mediated ERK activation mechanisms, integrating canonical and noncanonical signaling.

Keywords:
Cross talkERKG-proteinMAP kinaseβ-Arrestin

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Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Biochemistry

Background:

  • G protein-coupled receptors (GPCRs), characterized by their 7-transmembrane (7-TM) structure, are crucial cell surface receptors involved in diverse physiological responses.
  • Their serpentine structure allows interaction with various stimuli and facilitates the formation of multimeric protein complexes, contributing to signaling diversity.
  • GPCRs exhibit a wide range of subtypes and differential coupling to G-protein subunits and other proteins, enabling multistate activation and complex cellular responses.

Purpose of the Study:

  • To review the current understanding of mechanisms underlying ERK (extracellular signal-regulated kinase) activation downstream of GPCRs.
  • To explore both receptor-dependent and receptor-independent pathways involved in GPCR-mediated MAPK (mitogen-activated protein kinase) activation.
  • To highlight the functional integration of multiple pathways in GPCR-mediated cross-activation of MAPK signaling.

Main Methods:

  • Literature review of existing research on GPCR signaling and MAPK activation.
  • Analysis of studies investigating the cross-talk between GPCRs and MAPK pathways.
  • Synthesis of information on canonical and noncanonical signaling cascades initiated by GPCRs.

Main Results:

  • GPCRs can modulate canonical cellular responses as well as noncanonical pathways, including RTK and MAPK/ERK signaling.
  • GPCR-mediated activation of MAPK signaling is crucial for cell fate determination, affecting proliferation, apoptosis, and survival.
  • Evidence suggests functional integration of multiple pathways is involved in GPCR-mediated cross-activation of MAPK.

Conclusions:

  • GPCRs play a significant role in regulating MAPK/ERK signaling through various mechanisms.
  • Understanding these cross-activations is vital for comprehending cell fate determination processes.
  • Further research is needed to fully elucidate the complexities of receptor-dependent and -independent MAPK activation cascades downstream of GPCRs.