Regulatory effects of GRK2 on GPCRs and possible use as a drug target

Chen-chen HAN,Yang MA,Yi-fan LI,Yang WANG,Wei WEI

(Institute of Clinical Pharmacology,Anhui Medical University,Key Laboratory of Anti-inflammatory and Immune Medicine,Ministry of Education,Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine,Hefei 230032,China）

T1-13

Regulatory effects of GRK2 on GPCRs and possible use as a drug target

Chen-chen HAN,Yang MA,Yi-fan LI,Yang WANG,Wei WEI

(Institute of Clinical Pharmacology,Anhui Medical University,Key Laboratory of Anti-inflammatory and Immune Medicine,Ministry of Education,Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine,Hefei 230032,China）

Gprotein-coupled receptor kinase 2(GRK2),as a key Ser/Thr protein kinase,belong to the member of the Gprotein-coupled receptor kinase(GRK)family.The C-terminus of GRK2 including a plekstrin homology domain and the N-terminus of GRK2 including the RGS homology domain with binding sites for several proteins and lipids such as Gprotein-coupled receptors(GPCRs),Gprotein,phospholipase C,phosphatidylinositol 4,5-bisphosphate,extracellular signal-regulated kinase,protein kinase A and Gβγ,which can regulate the activity of GRK2.GRK2 can regulate GPCR desensitization and internalization by phosphorylating the GPCR,promoting the affinity of binding to arrestins,and uncoupling the receptors from Gproteins,which play an important role in maintaining the balance between the receptors and signal transduction.Previous studies have indicated that cardiac GRK2 overexpression can promote the phosphorylation of β-adrenergic receptor(βAR)leading to βAR desen?sitization and internalization,which play a pivotal role in inducing heart failure(HF)-related dysfunction and myocyte death.GRK2,as a regulator of cell function,is overexpression in hypertension.Overex?pression GRK2 can inhibit Akt/eNOS signaling pathway and decreased the production and activation of eNOS leading to endothelial dysfunction.Collagen-induced arthritis induces the upregulation of GRK2 expression in fibroblast-like synoviocytes.In this review,we mainly discussed the evidence for the association between GRK2 overexpression and various diseases,which suggests that GRK2 may be an effective drug target for preventing and treating heart failure,hypertension and inflammatory disease.

Gprotein-coupled receptor kinase 2;Gprotein-coupled receptor;signal transduction;drug targets;disease

The project supported by National Natural Science Foundation of China(81502123;81330081);NaturalScienceFoundationofAnhuiProvince(1308085QH130);andProvincialNaturalScienceResearch Foundation of Anhui Province(KJ2014A119)

Wei WEI;Tel:13605510563;E-mail：wwei@ahmu.edu.cn