Last update 01 Nov 2024

GRK2

Last update 01 Nov 2024

Basic Info

Synonyms

ADRBK1, adrenergic, beta, receptor kinase 1, BARK

+ [6]

Introduction

Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them (PubMed:19715378). Key regulator of LPAR1 signaling (PubMed:19306925). Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor (PubMed:19306925). Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner (PubMed:19306925). Positively regulates ciliary smoothened (SMO)-dependent Hedgehog (Hh) signaling pathway by facilitating the trafficking of SMO into the cilium and the stimulation of SMO activity (By similarity). Inhibits relaxation of airway smooth muscle in response to blue light (PubMed:30284927).

Drugs associated with GRK2

GSK-180736A

Target

GRK2 x ROCK1

Mechanism

GRK2 inhibitors [+1]

Active Org.

GlaxoSmithKline LLC

Originator Org.

GlaxoSmithKline LLC

Active Indication

Heart Failure

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

CCG-224406

Target

GRK2

Mechanism

GRK2 inhibitors

Active Org.

Temple University Graduate School

Originator Org.

Temple University Graduate School

Active Indication

Heart Failure

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

GSK2163632A

Target

GRK2 x IGF-1

Mechanism

GRK2 inhibitors [+1]

Active Org.

University of Michigan [+1]

Originator Org.

University of Minnesota [+1]

Active Indication

Heart Failure

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GRK2

100 Translational Medicine associated with GRK2

0 Patents (Medical) associated with GRK2

2,214

Literatures (Medical) associated with GRK2

01 Dec 2024·Animal Bioscience

Investigation of single nucleotide polymorphisms in differentially expressed genes and proteins reveals the genetic basis of skeletal muscle growth differences between Tibetan and Large White pigs

Article

Author: Xiong, Heli ; Zhang, Yan ; Zhao, Zhiyong

Objective: Skeletal muscle growth is an important economic trait for meat production, with notable differences between Tibetan pigs (TIBPs, a slow-growing breed) and Large White pigs (LWPs, a fast-growing breed). However, the genetic underpinnings of this disparity remain unclear.Methods: In the current study, we integrated differentially expressed genes (DEGs) and proteins (DEPs) from 60-day-old embryonic muscle tissue, along with whole-genome single nucleotide polymorphisms (SNPs) displaying absolute allele frequency differences (ΔAF) of 0.5 or more between the TIBP and LWP breeds, to unravel the genetic factors influencing skeletal muscle growth.Results: Our analysis revealed 3,499 DEGs and 628 DEPs with SNPs having a ΔAF equal to or greater than 0.5. Further functional analysis identified 145 DEGs and 23 DEPs involved in biological processes related to skeletal muscle development, and 22 DEGs and 3 DEPs implicated in the mechanistic target of rapamycin kinase signaling pathway, which is known for positively regulating protein synthesis. Among these genes, several DEGs and DEPs, enriched with TIPB-specific SNPs in regulatory or/and coding regions, showed marked ΔAF between the TIBP and LWP breeds, including MYF5, MYOF, ASB2, PDE9A, SDC1, PDGFRA, MYOM2, ACVR1, ZIC3, COL11A1, TGFBR1, EDNRA, TGFB2, PDE4D, PGAM2, GRK2, SCN4B, CACNA1S, MYL4, IGF1, and FOXO1. Additionally, genes such as CAPN3, MYOM2, and PGAM2, identified as both DEPs and DEGs related to skeletal muscle development, contained multiple TIBP-specific and LWP-predominant SNPs in regulatory and/or coding regions, underscoring significant ΔAF differences between the two breeds.Conclusion: This comprehensive investigation of SNPs in DEGs and DEPs identified a significant number of SNPs and genes related to skeletal muscle development during the prenatal stage. These findings not only shed light on potential causal genes for muscle divergence between the TIBP and LWP breeds but also offer valuable insights for pig breeding strategies aimed at enhancing meat production.

01 Dec 2024·Clinical Proteomics

Kinome and phosphoproteome reprogramming underlies the aberrant immune responses in critically ill COVID-19 patients

Article

Author: Van Nynatten, Logan Robert ; Kaneko, Tomonori ; Abdo, Rober ; Zhong, Shanshan ; Slessarev, Marat ; Fraser, Douglas D ; Ye, Mingliang ; Li, Shawn Shun-Cheng ; Ezra, Sally ; Hovey, Owen ; Voss, Courtney ; Liu, Xuguang

AbstractSARS-CoV-2 infection triggers extensive host immune reactions, leading to severe diseases in certain individuals. However, the molecular basis underlying the excessive yet non-productive immune responses in severe COVID-19 remains incompletely understood. In this study, we conducted a comprehensive analysis of the peripheral blood mononuclear cell (PBMC) proteome and phosphoproteome in sepsis patients positive or negative for SARS-CoV-2 infection, as well as healthy subjects, using quantitative mass spectrometry. Our findings demonstrate dynamic changes in the COVID-19 PBMC proteome and phosphoproteome during disease progression, with distinctive protein or phosphoprotein signatures capable of distinguishing longitudinal disease states. Furthermore, SARS-CoV-2 infection induces a global reprogramming of the kinome and phosphoproteome, resulting in defective adaptive immune response mediated by the B and T lymphocytes, compromised innate immune responses involving the SIGLEC and SLAM family of immunoreceptors, and excessive cytokine-JAK-STAT signaling. In addition to uncovering host proteome and phosphoproteome aberrations caused by SARS-CoV-2, our work recapitulates several reported therapeutic targets for COVID-19 and identified numerous new candidates, including the kinases PKG1, CK2, ROCK1/2, GRK2, SYK, JAK2/3, TYK2, DNA-PK, PKCδ, and the cytokine IL-12.

01 Oct 2024·Mucosal Immunology

Git2 deficiency promotes MDSCs recruitment in intestine via NF-κB-CXCL1/CXCL12 pathway and ameliorates necrotizing enterocolitis

Article

Author: Wang, Yanyan ; Wang, Jian ; Cai, Wei ; Le, Huijuan ; Wu, Jin ; Gong, Zizhen ; Tian, Chunyan ; Zhu, Fangxinxing ; Zhou, Jiefei ; Li, Dan

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in preterm infants and the most common cause of neonatal death, whereas the molecular mechanism of intestinal injury remains unclear accompanied by deficiency of effective therapeutic approaches. GIT2 (G-protein-coupled receptor kinase interacting proteins 2) can affect innate and adaptive immunity and has been involved in multiple inflammatory disorders. In this study, we investigated whether GIT2 participates in the pathogenesis of NEC. Here we found that intestinal Git2 gene expression was significantly increased in NEC patients and NEC mice, which positively correlated with the tissue damage severity, and Git2 deficiency could potently protect against NEC development in mice. Mechanistically, Git2 gene knockout dramatically increased the recruitment of MDSCs in the intestine, and in vivo depletion of MDSCs almost completely abrogated the protective effect of Git2 deficiency on NEC. Moreover, Git2 deficiency induced MDSCs intestinal accumulation mainly relied on CXCL1/CXCL12 signaling, as evidenced by the significant increment of CXCL1 and CXCL12 levels in intestinal epithelium of Git2^-/- mice and dramatically decrease of MDSCs accumulation in intestine as well as increase of NEC severity upon treatment of CXCL1/CXCL12 pathway inhibitors. In addition, Git2 deficiency induced up-regulation of CXCL1 and CXCL12 is at least partially mediated through activating NF-κB signaling. Thus, our findings suggest that GIT2 is involved in the pathogenesis of NEC, and targeting GIT2 may be a potential preventive and therapeutic approach for NEC.

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GRK2

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