Abstract
The counter-regulatory effects of insulin and catecholamines on carbohydrate and lipid metabolism are well studied, whereas the details of insulin regulation of β adrenergic receptor (βAR) signaling pathway in heart remain unknown. Here, we characterize a novel signaling pathway of insulin receptor (IR) to G protein-coupled receptor kinase 2 (GRK2) in the heart. Insulin stimulates recruitment of GRK2 to β2AR, which induces β2AR phosphorylation at the GRK sites of serine 355/356 and subsequently β2AR internalization. Insulin thereby suppresses βAR-induced cAMP-PKA activities and contractile response in neonatal and adult mouse cardiomyocytes. Deletion of insulin receptor substrate 2 (IRS2) disrupts the complex of IR and GRK2, which attenuates insulin-mediated β2AR phosphorylation at the GRK sites and β2AR internalization, and the counter-regulation effects of insulin on βAR signaling. These data indicate the requirements of IRS2 and GRK2 for insulin to stimulate counter-regulation of βAR via β2AR phosphorylation and internalization in cardiomyocytes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 707-715 |
| Number of pages | 9 |
| Journal | Cellular Signalling |
| Volume | 27 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2015 |
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Keywords
- Adrenergic receptor
- CAMP
- Cardiac contractility
- GRK2
- Insulin receptor
- Internalization
ASJC Scopus subject areas
- Cell Biology
Cite this
Insulin induces IRS2-dependent and GRK2-mediated β2AR internalization to attenuate βAR signaling in cardiomyocytes. / Fu, Qin; Xu, Bing; Parikh, Dippal; Cervantes, David; Xiang, Yang Kevin.
In: Cellular Signalling, Vol. 27, No. 3, 01.03.2015, p. 707-715.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Insulin induces IRS2-dependent and GRK2-mediated β2AR internalization to attenuate βAR signaling in cardiomyocytes
AU - Fu, Qin
AU - Xu, Bing
AU - Parikh, Dippal
AU - Cervantes, David
AU - Xiang, Yang Kevin
PY - 2015/3/1
Y1 - 2015/3/1
N2 - The counter-regulatory effects of insulin and catecholamines on carbohydrate and lipid metabolism are well studied, whereas the details of insulin regulation of β adrenergic receptor (βAR) signaling pathway in heart remain unknown. Here, we characterize a novel signaling pathway of insulin receptor (IR) to G protein-coupled receptor kinase 2 (GRK2) in the heart. Insulin stimulates recruitment of GRK2 to β2AR, which induces β2AR phosphorylation at the GRK sites of serine 355/356 and subsequently β2AR internalization. Insulin thereby suppresses βAR-induced cAMP-PKA activities and contractile response in neonatal and adult mouse cardiomyocytes. Deletion of insulin receptor substrate 2 (IRS2) disrupts the complex of IR and GRK2, which attenuates insulin-mediated β2AR phosphorylation at the GRK sites and β2AR internalization, and the counter-regulation effects of insulin on βAR signaling. These data indicate the requirements of IRS2 and GRK2 for insulin to stimulate counter-regulation of βAR via β2AR phosphorylation and internalization in cardiomyocytes.
AB - The counter-regulatory effects of insulin and catecholamines on carbohydrate and lipid metabolism are well studied, whereas the details of insulin regulation of β adrenergic receptor (βAR) signaling pathway in heart remain unknown. Here, we characterize a novel signaling pathway of insulin receptor (IR) to G protein-coupled receptor kinase 2 (GRK2) in the heart. Insulin stimulates recruitment of GRK2 to β2AR, which induces β2AR phosphorylation at the GRK sites of serine 355/356 and subsequently β2AR internalization. Insulin thereby suppresses βAR-induced cAMP-PKA activities and contractile response in neonatal and adult mouse cardiomyocytes. Deletion of insulin receptor substrate 2 (IRS2) disrupts the complex of IR and GRK2, which attenuates insulin-mediated β2AR phosphorylation at the GRK sites and β2AR internalization, and the counter-regulation effects of insulin on βAR signaling. These data indicate the requirements of IRS2 and GRK2 for insulin to stimulate counter-regulation of βAR via β2AR phosphorylation and internalization in cardiomyocytes.
KW - Adrenergic receptor
KW - CAMP
KW - Cardiac contractility
KW - GRK2
KW - Insulin receptor
KW - Internalization
UR - http://www.scopus.com/inward/record.url?scp=84922594993&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84922594993&partnerID=8YFLogxK
U2 - 10.1016/j.cellsig.2014.11.018
DO - 10.1016/j.cellsig.2014.11.018
M3 - Article
C2 - 25460042
AN - SCOPUS:84922594993
VL - 27
SP - 707
EP - 715
JO - Cellular Signalling
JF - Cellular Signalling
SN - 0898-6568
IS - 3
ER -