Homocysteine effects classical pathway of GPCR down regulation

q/11, Gα12/13, Gi/o

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

Research output: Contribution to journalArticle

3 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Homocysteine
G-Protein-Coupled Receptors
Down-Regulation
Gq-G11 GTP-Binding Protein alpha Subunits
Signal transduction
Phosphorylation
Pertussis Toxin
Endothelial cells
GTP-Binding Proteins
Actins
Signal Transduction
Endothelial Cells
Western Blotting
Chemical activation

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

Cite this

Homocysteine effects classical pathway of GPCR down regulation : Gαq/11, Gα12/13, Gi/o. / Vacek, T. P.; Sen, U.; Tyagi, N.; Mishra, Paras Kumar; Moshal, K. S.; Passmore, J. C.; Tyagi, Suresh C.

In: Molecular and Cellular Biochemistry, Vol. 321, No. 1-2, 01.01.2009, p. 1-8.

Research output: Contribution to journalArticle

Vacek, T. P. ; Sen, U. ; Tyagi, N. ; Mishra, Paras Kumar ; Moshal, K. S. ; Passmore, J. C. ; Tyagi, Suresh C. / Homocysteine effects classical pathway of GPCR down regulation : Gαq/11, Gα12/13, Gi/o. In: Molecular and Cellular Biochemistry. 2009 ; Vol. 321, No. 1-2. pp. 1-8.
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