Activation of ERK, JNK, Akt, and G-protein coupled signaling by hybrid angiotensin II AT1/bradykinin B2 receptors expressed in HEK-293 cells
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Activation of ERK, JNK, Akt, and G-protein coupled signaling by hybrid angiotensin II AT1/bradykinin B2 receptors expressed in HEK-293 cells. / Yu, Jun; Lubinsky, David; Tsomaia, Natia; Huang, Zhenhua; Taylor, Linda; Mierke, Dale; Navarro, Javier; Mirza, Osman Asghar; Polgar, Peter.
In: Journal of Cellular Biochemistry, Vol. 101, No. 1, 2007, p. 192-204.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Activation of ERK, JNK, Akt, and G-protein coupled signaling by hybrid angiotensin II AT1/bradykinin B2 receptors expressed in HEK-293 cells
AU - Yu, Jun
AU - Lubinsky, David
AU - Tsomaia, Natia
AU - Huang, Zhenhua
AU - Taylor, Linda
AU - Mierke, Dale
AU - Navarro, Javier
AU - Mirza, Osman Asghar
AU - Polgar, Peter
N1 - Keywords: Amino Acid Sequence; Arachidonic Acid; Calcium; Cell Line; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; GTP-Binding Proteins; Humans; Kinetics; Ligands; MAP Kinase Kinase 4; Models, Molecular; Molecular Sequence Data; Mutagenesis, Site-Directed; Phosphatidylinositols; Phosphorylation; Protein Binding; Protein Structure, Secondary; Protein Structure, Tertiary; Proto-Oncogene Proteins c-akt; Receptor, Angiotensin, Type 1; Receptor, Bradykinin B2; Sequence Analysis, DNA; Signal Transduction; Transfection
PY - 2007
Y1 - 2007
N2 - 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, Galphai/Galphaq, linked signaling. Computer based molecular models suggested that Ser-Met-Gly from the IC2 of the BKB2R is detrimental for the Galphai/Galphaq coupled functions of this hybrid. The return of Lys-Ser-Arg of the AT1R to this hybrid led to almost full recovery of Galphai and Galphaq 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.
AB - 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, Galphai/Galphaq, linked signaling. Computer based molecular models suggested that Ser-Met-Gly from the IC2 of the BKB2R is detrimental for the Galphai/Galphaq coupled functions of this hybrid. The return of Lys-Ser-Arg of the AT1R to this hybrid led to almost full recovery of Galphai and Galphaq 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.
KW - Former Faculty of Pharmaceutical Sciences
U2 - 10.1002/jcb.21161
DO - 10.1002/jcb.21161
M3 - Journal article
C2 - 17212359
VL - 101
SP - 192
EP - 204
JO - Journal of cellular biochemistry. Supplement
JF - Journal of cellular biochemistry. Supplement
SN - 0733-1959
IS - 1
ER -
ID: 11638879