GRK2 at the Control Shaft of Cellular Metabolism

Michele      Ciccarelli; Ersilia      Cipolletta; Guido      Iaccarino

Abstract

G protein receptor kinase 2 (GRK2) has been for years mainly considered the negative regulator of the cardiac β adrenergic signaling. However GRK2 is a ubiquitous molecule and its kinase activity and scaffold properties brought to several investigations which have evidenced its involvement in pathophysiology of extra-cardiac diseases. Later discoveries, moreover, indicated that this molecule is also able to influence other pathways such as insulin signaling by an inhibitory role similar to what described years before on βAR signaling. The importance of this novel function is in particular related to the possibility that this molecule can regulate the cellular metabolism, modifying the ability of cells to utilize different substrates. This hypothesis has been recently investigated in animal model of Heart Failure, evidencing that upregulation of GRK2 leads to alterations of cardiac glucose metabolism in the early stages of the disease. However GRK2 shows increased level also in the early stages of others chronic disease such as Alzheimers Disease, indicating that these findings could be possibly applied to others cellular system and supporting the emerging idea of GRK2 as master regulator of cellular metabolism.

Keywords: Metabolism, glucose, insulin signaling, chronic disease, G protein receptor kinase 2 (GRK2), Alzheimer's Disease, Myocardial ischemia, hypertension, energy homeostasis, oxidative stress