Molecule Information

General Information of the Molecule (ID: Mol00231)

• Name: Beta adrenoceptor kinase 1 (GRK2) ,Homo sapiens
• Synonyms: Beta-ARK-1; G-protein coupled receptor kinase 2; ADRBK1; BARK; BARK1
• Molecule Type: Protein
• Gene Name: GRK2
• Gene ID: 156
• Location: chr11:67266473-67286556[+]
• Sequence:
  MADLEAVLADVSYLMAMEKSKATPAARASKKILLPEPSIRSVMQKYLEDRGEVTFEKIFS
  QKLGYLLFRDFCLNHLEEARPLVEFYEEIKKYEKLETEEERVARSREIFDSYIMKELLAC
  SHPFSKSATEHVQGHLGKKQVPPDLFQPYIEEICQNLRGDVFQKFIESDKFTRFCQWKNV
  ELNIHLTMNDFSVHRIIGRGGFGEVYGCRKADTGKMYAMKCLDKKRIKMKQGETLALNER
  IMLSLVSTGDCPFIVCMSYAFHTPDKLSFILDLMNGGDLHYHLSQHGVFSEADMRFYAAE
  IILGLEHMHNRFVVYRDLKPANILLDEHGHVRISDLGLACDFSKKKPHASVGTHGYMAPE
  VLQKGVAYDSSADWFSLGCMLFKLLRGHSPFRQHKTKDKHEIDRMTLTMAVELPDSFSPE
  LRSLLEGLLQRDVNRRLGCLGRGAQEVKESPFFRSLDWQMVFLQKYPPPLIPPRGEVNAA
  DAFDIGSFDEEDTKGIKLLDSDQELYRNFPLTISERWQQEVAETVFDTINAETDRLEARK
  KAKNKQLGHEEDYALGKDCIMHGYMSKMGNPFLTQWQRRYFYLFPNRLEWRGEGEAPQSL
  LTMEEIQSVEETQIKERKCLLLKIRGGKQFILQCDSDPELVQWKKELRDAYREAQQLVQR
  VPKMKNKPRSPVVELSKVPLVQRGSANGL
• Function: Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them. Key regulator of LPAR1 signaling. Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor. Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner. 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. Inhibits relaxation of airway smooth muscle in response to blue light.
• Uniprot ID: ARBK1_HUMAN
• Ensembl ID: ENSG00000173020
• HGNC ID: HGNC:289

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Daunorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Leukemia [1]

• Resistant Disease: Leukemia [ICD-11: 2B33.6]
• Resistant Drug: Daunorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: HL60 cells; Peripheral blood; Homo sapiens (Human); CVCL_0002
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• Experiment for Molecule Alteration: Luciferase reporter assay; Western blot analysis
• Experiment for Drug Resistance: Luminescent cell viability assay
• Mechanism Description: miR125a mediated daunorubicin resistance in leukemia cell lines through the decrease of GRk2 and Puma which were proved to be direct targets of miR125a. Overexpression of miR125a induced drug resistance in HL-60, k562, and THP-1cell lines through reducing apoptosis.

Disease Class: Leukemia [2]

• Resistant Disease: Leukemia [ICD-11: 2B33.6]
• Resistant Drug: Daunorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• In Vitro Model: Jurkat cells; Pleural effusion; Homo sapiens (Human); CVCL_0065
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: REH cells; Bone marrow; Homo sapiens (Human); CVCL_1650
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Luminescent cell viability assay
• Mechanism Description: miR-125b downregulated GRk2 and PUMA, which inhibited apoptosis and induced leukemia cell resistance to DNR.

References

• Ref 1: Involvement of miR-125a in resistance to daunorubicin by inhibiting apoptosis in leukemia cell lines. Tumour Biol. 2017 Apr;39(4):1010428317695964. doi: 10.1177/1010428317695964.
• Ref 2: microRNA 125b promotes leukemia cell resistance to daunorubicin by inhibiting apoptosis. Mol Med Rep. 2014 May;9(5):1909-16. doi: 10.3892/mmr.2014.2011. Epub 2014 Mar 6.