Homocysteine effects classical pathway of GPCR down regulation: Gαq/11, Gα12/13, Gi/o

T. P. Vacek, U. Sen, N. Tyagi, M. Kumar, K. S. Moshal, J. C. Passmore, Suresh C. Tyagi

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

G protein-coupled receptors (GPCRs) are known to modulate intracellular effectors involved in cardiac function. We recently reported homocysteine (Hcy)-induced ERK-phosphorylation was suppressed by pertussis toxin (PTX), which suggested the involvement of GPCRs in initiating signal transduction. An activated GPCR undergoes down regulation via a known mechanism involving ERK, GRK2, β-arrestin1: ERK activity increases; GRK2 activity increases; β-arrestin1 is degraded. We hypothesized that Hcy treatment leads to GPCR activation and down regulation. Microvascular endothelial cells were treated with Hcy. Expression of phospho-ERK1 and phospho-GRK2 was determined using Western blot, standardized to ERK1, GRK2, and β-actin. Hcy was shown to dephosphorylate GRK2, thereby enhancing the activity. The results provided further evidence that Hcy acts as an agonist to activate GPCRs, followed by their down regulation. Hcy was also shown to decrease the content of the following G proteins and other proteins: β-arrestin1, Gαq/11, Gα12/13, Gi/o.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalMolecular and cellular biochemistry
Volume321
Issue number1-2
DOIs
StatePublished - Jan 1 2009

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Keywords

  • Desensitization
  • ERK1
  • G protein
  • GPCR
  • GRK2
  • Hcy
  • Heart failure
  • Homocysteine
  • c-Src
  • β-Arrestin1

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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