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Dopamine Receptors, Signaling Pathways, and Drugs
Published in Nira Ben-Jonathan, Dopamine, 2020
Both GRKs and β-arrestins have multiple functions beyond their roles in receptor desensitization. There are seven GRKs, which are subdivided into four subfamilies: (1) GRK1-like (1 and 7), (2) GRK2-like (2 and 3), (3) GRK4-like (4 and 5), and (4) GRK6. GRK1 and GRK7 are limited to the regulation of visual opsins, while GRK4 has some expression in the cerebellum, kidney and testes. GRK2, the most widely studied family member, phosphorylates non-receptor substrates and interacts with D1R- and D2R-initiated signaling cascades [41]. Both GRK2 and GRK4 have been implicated in the desensitization of renal D1R, one of the best studied peripheral DARs [42]. The renal dopaminergic system is covered in Chapter 7.
Melanoma Growth Stimulatory Activity: Physiology, Biology, Structure/Function, and Role in Disease
Published in Richard Horuk, Chemoattractant Ligands and Their Receptors, 2020
Ann Richmond, Rebecca L. Shattuck
For comparison, the fMLP receptor undergoes phosphorylation on serine and threonine residues and the kinase which is apparently involved in this phosphorylation event is the G-protein-coupled receptor kinase GRK2.112 For the fMLP receptor, there is an order of phosphorylation where residues 328 and 329 must be phosphorylated before 334 and 339. For fMLP, GRK3 has only 50% the activity that GRK2 exhibits. It has not yet been determined whether GRK is involved in the phosphorylation of the IL-8RB and, if so, which GRK is involved.
Physiological Properties of the Lower Urinary Tract
Published in Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George, The Scientific Basis of Urology, 2010
Desensitization of muscarinic receptors results in detrusor smooth muscle being less sensitive to nerve stimuli. This is mediated by phosphorylation of the muscarinic receptor by guanosine phosphate–binding G protein–coupled receptor kinase (GRK) (90); m2 and m3 GRK2 mRNAs have been described. Protein expression of GRK2 is significantly reduced in detrusor from patients with benign prostatic hyperplasia (91) and may therefore contribute to detrusor overactivity.
Case Report: Concurrent Clonidine Abuse and Opioid Use Disorder
Published in Journal of Psychoactive Drugs, 2021
Usual therapy for severe hypertension following clonidine withdrawal includes the alpha 1 antagonist prazosin and occasionally cardioselective beta-blockers and chlordiazepoxide hydrochloride (Mehta and Lopez 1987). However, beta-blocker administration may exaggerate the hypertensive response after clonidine withdrawal because of an increase in peripheral vascular resistance (Mehta and Lopez 1987). This exaggerated hypertensive response potentially occurred in our patient case since he was also receiving propranolol for tremors. Our cardiology consult service noted that G-protein-coupled receptor kinase 2 (GRK2) inhibition plays a role in attenuating some of this hypertensive response. It is believed that angiotensin receptor blockers have some role in blocking GRK2 activity, and this was noted as the reason why losartan was recommended by our cardiology consult service.
Exosomes derived from GIT1-overexpressing bone marrow mesenchymal stem cells promote traumatic spinal cord injury recovery in a rat model
Published in International Journal of Neuroscience, 2021
Yongjun Luo, Tao Xu, Wei Liu, Yuluo Rong, Jiaxing Wang, Jin Fan, Guoyong Yin, Weihua Cai
G protein-coupled receptor kinase 2 interacting protein 1 (GIT1), a multifunction and multidomain scaffold protein, was first identified for its binding to GRK2 and its effects on adrenergic receptor endocytosis [22]. It works as a regulation of cytoskeletal dynamics and an integrator of signaling pathways during cell spreading, adhesion and migration, receptor internalization, synapse formation and cytoskeletal organization [23–25]. Several studies have showed that GIT1 could regulate cardiac mitochondrial biogenesis, cell survival and is essential in stimulating intestinal epithelial restitution [26,27]. It was also demonstrated that GIT1 deficiency mice might have a chondrocyte differentiation and fracture-healing delay resulting from decreased revascularization and increased apoptosis [21,28,29].
TRH receptor mobility in the plasma membrane is strongly affected by agonist binding and by interaction with some cognate signaling proteins
Published in Journal of Receptors and Signal Transduction, 2018
Radka Moravcova, Barbora Melkes, Jiri Novotny
Whereas the observed decline of TRH receptor mobility due to agonist occupancy can be quite satisfyingly explained, it is not readily evident why its mobility should decrease after the diminishing of some signaling proteins. It is known that agonist stimulation of the TRH receptor is followed by GRK-mediated receptor phosphorylation and βArr recruitment [30]. Besides that these receptors can form dimers and we previously reported that agonist binding strongly promotes TRH receptor dimerization [14]. All these agonist-initiated events could well contribute to the reduction in TRH receptor mobility. GRK2 is a cytosolic protein uniquely targeted to the membrane from the cytoplasm in a signaling-dependent manner [31]. Therefore, it is perhaps not too surprising that decreased GRK2 expression did not significantly affect TRH receptor movement in the plasma membrane under resting conditions. However, it is much less clear why down-regulation of other signaling proteins (Gq/11α, Giα1, Gβ, βArr and PLCβ1) slowed down the rate of TRH receptor diffusion and/or reduced the receptor mobile fraction. It can be assumed that these proteins may have an indispensable role in TRH receptor organization in the plasma membrane and thus participate in the modulation of receptor lateral movement. Nonetheless, it remains to be determined why down-regulation of these proteins leads exclusively to a decrease in TRH receptor mobility. To sum up, this study indicates for the first time that the mobility of membrane-bound receptors can be distinctly affected by changes in abundance of different signaling proteins.