Activation of ERK, JNK, Akt, and G-protein coupled signaling by hybrid angiotensin II AT1/bradykinin B2 receptors expressed in HEK-293 cells

Jun Yu, David Lubinsky, Natia Tsomaia, Zhenhua Huang, Linda Taylor, Dale Mierke, Javier Navarro, Osman Miraz, Peter Polgar

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Bradykinin (BK) and angiotensin II (AngII) often have opposite roles in cardiovascular diseases. Our aim here was to construct hybrid receptors which bind AngII but signal as BK. Various sequences of the intracellular face of the AngII type I receptor, AT1R, were replaced with corresponding sequences from the bradykinin B2 receptor (BKB2R). The hybrids demonstrated a number of signaling characteristics of the BKB2R. For example, the hybrids demonstrated BK as opposed to AngII like phosphorylation of Akt and JNK. The hybrids containing the BKB2R intracellular loop 2 (IC2) displayed minimal G-protein, Gαi/Gαq, linked signaling. Computer based molecular models suggested that Ser-Met-Gly from the IC2 of the BKB2R is detrimental for the Gαi/Gαq coupled functions of this hybrid. The return of Lys-Ser-Arg of the AT1R to this hybrid led to almost full recovery of Gαd and Gαq activation. The design and production of AT1/BKB2 hybrid receptors is a potential approach in the treatment of hypertension related diseases where the presence of AngII, its AT1 receptor and the consequent signal transduction has proven detrimental.

Original languageEnglish (US)
Pages (from-to)192-204
Number of pages13
JournalJournal of Cellular Biochemistry
Volume101
Issue number1
DOIs
StatePublished - May 1 2007

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Keywords

  • Akt
  • Angiotensin II type I receptor
  • Bradykinin B2 receptor
  • Chimeric receptor
  • GPCR
  • MAPK
  • Molecular modeling
  • Signal transduction

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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