Beta adrenergic receptor kinase-2: Difference between revisions

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{{Infobox_gene}}
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
'''Beta-adrenergic receptor kinase 2''' (beta-ARK-2) also known as '''G-protein-coupled receptor kinase 3''' (GRK3) is an [[enzyme]] that in humans is encoded by the ''ADRBK2'' [[gene]].<ref name="pmid7695743">{{cite journal | vauthors = Calabrese G, Sallese M, Stornaiuolo A, Stuppia L, Palka G, De Blasi A | title = Chromosome mapping of the human arrestin (SAG), beta-arrestin 2 (ARRB2), and beta-adrenergic receptor kinase 2 (ADRBK2) genes | journal = Genomics | volume = 23 | issue = 1 | pages = 286–8 |date=Feb 1995 | pmid = 7695743 | pmc =  | doi = 10.1006/geno.1994.1497 }}</ref><ref name="entrez" />
{{GNF_Protein_box
| image =
| image_source = 
| PDB =  
| Name = Adrenergic, beta, receptor kinase 2
| HGNCid = 290
| Symbol = ADRBK2
| AltSymbols =; BARK2; GRK3
| OMIM = 109636
| ECnumber =
| Homologene = 21072
| MGIid = 87941
  | GeneAtlas_image1 = PBB_GE_ADRBK2_204184_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_ADRBK2_204183_s_at_tn.png
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0004703 |text = G-protein coupled receptor kinase activity}} {{GNF_GO|id=GO:0004871 |text = signal transducer activity}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0016740 |text = transferase activity}}
| Component =
| Process = {{GNF_GO|id=GO:0006468 |text = protein amino acid phosphorylation}} {{GNF_GO|id=GO:0007165 |text = signal transduction}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 157
    | Hs_Ensembl = ENSG00000100077
    | Hs_RefseqProtein = NP_005151
    | Hs_RefseqmRNA = NM_005160
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 22
    | Hs_GenLoc_start = 24290946
    | Hs_GenLoc_end = 24449916
    | Hs_Uniprot = P35626
    | Mm_EntrezGene = 320129
    | Mm_Ensembl = ENSMUSG00000042249
    | Mm_RefseqmRNA = NM_001035531
    | Mm_RefseqProtein = NP_001030608
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 5
    | Mm_GenLoc_start = 113150781
    | Mm_GenLoc_end = 113255817
    | Mm_Uniprot = Q8BVT9
  }}
}}


'''Adrenergic, beta, receptor kinase 2''', also known as '''ADRBK2''', is a human [[gene]].<ref name="entrez" />
== Function ==
The beta-adrenergic receptor kinase specifically [[phosphorylation|phosphorylates]] the agonist-occupied form of the [[adrenergic receptor|beta-adrenergic]] and related [[G protein-coupled receptor]]s. Overall, the beta adrenergic receptor kinase 2 has 85% amino acid similarity with [[beta adrenergic receptor kinase|beta adrenergic receptor kinase 1]], with the protein kinase catalytic domain having 95% similarity. These data suggest the existence of a family of [[beta-adrenergic-receptor kinase|receptor kinases]] which may serve broadly to regulate receptor function.<ref name="entrez">{{cite web | title = Entrez Gene: ADRBK2 adrenergic, beta, receptor kinase 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=157| accessdate = }}</ref>


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== Discovery ==
{{PBB_Summary
The beta adrenergic receptor kinase-2 was cloned from mice and rats in 1991<ref name="pmid1869533">{{cite journal | vauthors = Benovic JL, Onorato JJ, Arriza JL, Stone WC, Lohse M, Jenkins NA, Gilbert DJ, Copeland NG, Caron MG, Lefkowitz RJ | title = Cloning, expression, and chromosomal localization of beta-adrenergic receptor kinase 2. A new member of the receptor kinase family | journal = J. Biol. Chem. | volume = 266 | issue = 23 | pages = 14939–46 |date=August 1991 | pmid = 1869533 | doi = | url =  }}</ref> and the human gene was cloned in 1993.<ref name="pmid8427589">{{cite journal | vauthors = Parruti G, Ambrosini G, Sallese M, De Blasi A | title = Molecular cloning, functional expression and mRNA analysis of human beta-adrenergic receptor kinase 2 | journal = Biochem. Biophys. Res. Commun. | volume = 190 | issue = 2 | pages = 475–81 |date=January 1993 | pmid = 8427589 | doi = 10.1006/bbrc.1993.1072 | url =  }}</ref>
| section_title =  
| summary_text = The beta-adrenergic receptor kinase specifically phosphorylates the agonist-occupied form of the beta-adrenergic and related G protein-coupled receptors. Overall, the beta adrenergic receptor kinase 2 has 85% amino acid similarity with beta adrenergic receptor kinase 1, with the protein kinase catalytic domain having 95% similarity. These data suggest the existence of a family of receptor kinases which may serve broadly to regulate receptor function.<ref name="entrez">{{cite web | title = Entrez Gene: ADRBK2 adrenergic, beta, receptor kinase 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=157| accessdate = }}</ref>
}}


Beta adrenergic receptor kinase-2 (ARBK2, BARK-2, G-protein-coupled receptor kinase 3, GRK3) is an intracellular enzyme that phosphorylates [[G protein-coupled receptor|G protein-coupled receptors]].  It was cloned from mice and rats in 1991,<ref>{{cite journal
== Clinical significance ==
  | last = Benovic
  | first = J. L.
  | authorlink =
  | coauthors =
  | title = "Cloning, expression, and chromosomal localization of beta-adrenergic receptor kinase 2: a new member of the receptor kinase family"
  | journal = J. Biol. Chem.
  | volume = 266
  | issue =
  | pages = 14939-14946
  | publisher =
  | date = 1991
  | url =
  | doi =
  | id =
  | accessdate =  }}</ref>.  The human gene was cloned in 1993.<ref>{{cite journal
  | last = Parruti
  | first = G.
  | authorlink =
  | coauthors =
  | title = "Molecular cloning, functional expression and mRNA analysis of human beta-adrenergic receptor kinase 2."
  | journal = Biochem. Biophys. Res. Commun.
  | volume = 190
  | issue =
  | pages = 475-481
  | publisher =
  | date = 1993
  | url =
  | doi =
  | id =
  | accessdate =  }}</ref>


In 2003, a group of American and Canadian researchers published a paper that used [[Genetic linkage|gene linkage]] techniques to identify a mutation in the '''GRK3''' gene as a possible cause of up to 10% of cases of [[bipolar disorder]].<ref>{{cite journal
[[Genetic linkage|Gene linkage]] techniques were used to identify a mutation in the ''GRK3'' gene as a possible cause of up to 10% of cases of [[bipolar disorder]].<ref name="pmid12808434">{{cite journal | vauthors = Barrett TB, Hauger RL, Kennedy JL, Sadovnick AD, Remick RA, Keck PE, McElroy SL, Alexander M, Shaw SH, Kelsoe JR | title = Evidence that a single nucleotide polymorphism in the promoter of the G protein receptor kinase 3 gene is associated with bipolar disorder | journal = Mol. Psychiatry | volume = 8 | issue = 5 | pages = 546–57 |date=May 2003 | pmid = 12808434 | doi = 10.1038/sj.mp.4001268 | url =  }}</ref> Beta adrenergic receptor kinase-2 appears to affect [[dopamine]] metabolism.  Subsequent studies, while noting that chromosome 22q12 may harbor a risk gene for [[schizophrenia]], did not find that the gene coding for beta adrenergic receptor kinase-2 was linked to schizophrenia.<ref name="pmid15006433">{{cite journal | vauthors = Yu SY, Takahashi S, Arinami T, Ohkubo T, Nemoto Y, Tanabe E, Fukura Y, Matsuura M, Han YH, Zhou RL, Shen YC, Matsushima E, Kojima T | title = Mutation screening and association study of the beta-adrenergic receptor kinase 2 gene in schizophrenia families | journal = Psychiatry Res | volume = 125 | issue = 2 | pages = 95–104 |date=February 2004 | pmid = 15006433 | doi = 10.1016/j.psychres.2003.12.003 | url =  }}</ref>
  | last = Barrett
<!--To do: which chromosome, what pathways, explain the biology a bit-->
  | first = T B
  | authorlink =
  | coauthors =
  | title = "Evidence that a single nucleotide polymorphism in the promoter of the G protein receptor kinase 3 gene is associated with bipolar disorder"
  | journal = Molecular Psychiatry
  | volume = 8
  | issue =
  | pages = 546-557
  | publisher =
  | date = 2003
  | url =
  | doi =
  | id =
  | accessdate =  }}</ref> Beta adrenergic receptor kinase-2 appears to affect [[dopamine]] metabolism.   


Subsequent studies, while noting that chromosome 22q12 may harbor a risk gene for [[schizophrenia]], did not find that the gene coding for beta adrenergic receptor kinase-2 was linked to schizophrenia.<ref>{{cite journal
It has been associated with [[WHIM syndrome]].<ref name="pmid18274673">{{cite journal |author=Balabanian K |title=Leukocyte analysis from WHIM syndrome patients reveals a pivotal role for GRK3 in CXCR4 signaling |journal=J. Clin. Invest. |volume=118 |issue=3 |pages=1074–84 |date=March 2008 |pmid=18274673 |pmc=2242619 |doi=10.1172/JCI33187 |name-list-format=vanc|author2=Levoye A |author3=Klemm L |display-authors=3 |last4=Lagane |first4=Bernard |last5=Hermine |first5=Olivier |last6=Harriague |first6=Julie |last7=Baleux |first7=Françoise |last8=Arenzana-Seisdedos |first8=Fernando |last9=Bachelerie |first9=Françoise }}</ref>
  | last = Yu
  | first = SY
  | authorlink =
  | coauthors =
  | title = "Mutation screening and association study of the beta-adrenergic receptor kinase 2 gene in schizophrenia families."
  | journal = Psychiatry Res.
  | volume = 125
  | issue =
  | pages = 95-104
  | publisher =
  | date = 2004
  | url =  
  | doi =
  | id =  
  | accessdate = }}</ref>
 
<!--To do: which chromosome, what pathways, explain the biology a bit-->


==References==
==References==
{{reflist|2}}
{{reflist}}


==Further reading==
==Further reading==
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{{PBB_Further_reading  
{{PBB_Further_reading  
| citations =  
| citations =  
*{{cite journal  | author=Benovic JL, Onorato JJ, Arriza JL, ''et al.'' |title=Cloning, expression, and chromosomal localization of beta-adrenergic receptor kinase 2. A new member of the receptor kinase family. |journal=J. Biol. Chem. |volume=266 |issue= 23 |pages= 14939-46 |year= 1991 |pmid= 1869533 |doi=  }}
*{{cite journal  | author=Benovic JL |title=Cloning, expression, and chromosomal localization of beta-adrenergic receptor kinase 2. A new member of the receptor kinase family |journal=J. Biol. Chem. |volume=266 |issue= 23 |pages= 14939–46 |year= 1991 |pmid= 1869533 |doi=  |name-list-format=vanc| author2=Onorato JJ | author3=Arriza JL  | display-authors=3  | last4=Stone  | first4=WC  | last5=Lohse  | first5=M | last6=Jenkins  | first6=NA  | last7=Gilbert  | first7=DJ  | last8=Copeland  | first8=NG  | last9=Caron  | first9=MG  }}
*{{cite journal | author=Calabrese G, Sallese M, Stornaiuolo A, ''et al.'' |title=Chromosome mapping of the human arrestin (SAG), beta-arrestin 2 (ARRB2), and beta-adrenergic receptor kinase 2 (ADRBK2) genes. |journal=Genomics |volume=23 |issue= 1 |pages= 286-8 |year= 1995 |pmid= 7695743 |doi= 10.1006/geno.1994.1497 }}
*{{cite journal  | vauthors=Parruti G, Ambrosini G, Sallese M, De Blasi A |title=Molecular cloning, functional expression and mRNA analysis of human beta-adrenergic receptor kinase 2 |journal=Biochem. Biophys. Res. Commun. |volume=190 |issue= 2 |pages= 475–81 |year= 1993 |pmid= 8427589 |doi=10.1006/bbrc.1993.1072  }}
*{{cite journal  | author=Parruti G, Ambrosini G, Sallese M, De Blasi A |title=Molecular cloning, functional expression and mRNA analysis of human beta-adrenergic receptor kinase 2. |journal=Biochem. Biophys. Res. Commun. |volume=190 |issue= 2 |pages= 475-81 |year= 1993 |pmid= 8427589 |doi= }}
*{{cite journal  | vauthors=Oppermann M, Freedman NJ, Alexander RW, Lefkowitz RJ |title=Phosphorylation of the type 1A angiotensin II receptor by G protein-coupled receptor kinases and protein kinase C |journal=J. Biol. Chem. |volume=271 |issue= 22 |pages= 13266–72 |year= 1996 |pmid= 8662816 |doi=10.1074/jbc.271.22.13266 }}
*{{cite journal  | author=Oppermann M, Freedman NJ, Alexander RW, Lefkowitz RJ |title=Phosphorylation of the type 1A angiotensin II receptor by G protein-coupled receptor kinases and protein kinase C. |journal=J. Biol. Chem. |volume=271 |issue= 22 |pages= 13266-72 |year= 1996 |pmid= 8662816 |doi=  }}
*{{cite journal  | author=Premont RT |title=β2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue= 24 |pages= 14082–7 |year= 1998 |pmid= 9826657 |doi=10.1073/pnas.95.24.14082 | pmc=24330 |name-list-format=vanc| author2=Claing A  | author3=Vitale N  | display-authors=3  | last4=Freeman  | first4=JL  | last5=Pitcher  | first5=JA  | last6=Patton  | first6=WA  | last7=Moss | first7=J | last8=Vaughan  | first8=M  | last9=Lefkowitz  | first9=RJ  }}
*{{cite journal  | author=Premont RT, Claing A, Vitale N, ''et al.'' |title=beta2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue= 24 |pages= 14082-7 |year= 1998 |pmid= 9826657 |doi=  }}
*{{cite journal  | vauthors=Oppermann M, Mack M, Proudfoot AE, Olbrich H |title=Differential effects of CC chemokines on CC chemokine receptor 5 (CCR5) phosphorylation and identification of phosphorylation sites on the CCR5 carboxyl terminus |journal=J. Biol. Chem. |volume=274 |issue= 13 |pages= 8875–85 |year= 1999 |pmid= 10085131 |doi=10.1074/jbc.274.13.8875  }}
*{{cite journal | author=Oppermann M, Mack M, Proudfoot AE, Olbrich H |title=Differential effects of CC chemokines on CC chemokine receptor 5 (CCR5) phosphorylation and identification of phosphorylation sites on the CCR5 carboxyl terminus. |journal=J. Biol. Chem. |volume=274 |issue= 13 |pages= 8875-85 |year= 1999 |pmid= 10085131 |doi=  }}
*{{cite journal  | author=Dunham I |title=The DNA sequence of human chromosome 22 |journal=Nature |volume=402 |issue= 6761 |pages= 489–95 |year= 1999 |pmid= 10591208 |doi= 10.1038/990031  |name-list-format=vanc| author2=Shimizu N  | author3=Roe BA  | display-authors=3  | last4=Bruskiewich | first4=R. | last5=Beare  | first5=D. M. | last6=Clamp  | first6=M.  | last7=Smink  | first7=L. J.  | last8=Ainscough  | first8=R. | last9=Almeida  | first9=J. P. }}
*{{cite journal | author=Dunham I, Shimizu N, Roe BA, ''et al.'' |title=The DNA sequence of human chromosome 22. |journal=Nature |volume=402 |issue= 6761 |pages= 489-95 |year= 1999 |pmid= 10591208 |doi= 10.1038/990031 }}
*{{cite journal  | vauthors=Inngjerdingen M, Damaj B, Maghazachi AA |title=Human NK cells express CC chemokine receptors 4 and 8 and respond to thymus and activation-regulated chemokine, macrophage-derived chemokine, and I-309 |journal=J. Immunol. |volume=164 |issue= 8 |pages= 4048–54 |year= 2000 |pmid= 10754297 |doi= 10.4049/jimmunol.164.8.4048}}
*{{cite journal  | author=Inngjerdingen M, Damaj B, Maghazachi AA |title=Human NK cells express CC chemokine receptors 4 and 8 and respond to thymus and activation-regulated chemokine, macrophage-derived chemokine, and I-309. |journal=J. Immunol. |volume=164 |issue= 8 |pages= 4048-54 |year= 2000 |pmid= 10754297 |doi= }}
*{{cite journal  | author=Celver JP |title=Threonine 180 is required for G-protein-coupled receptor kinase 3- and beta-arrestin 2-mediated desensitization of the mu-opioid receptor in Xenopus oocytes |journal=J. Biol. Chem. |volume=276 |issue= 7 |pages= 4894–900 |year= 2001 |pmid= 11060299 |doi= 10.1074/jbc.M007437200 |name-list-format=vanc| author2=Lowe J | author3=Kovoor A  | display-authors=3  | last4=Gurevich  | first4=VV  | last5=Chavkin  | first5=C }}
*{{cite journal  | author=Celver JP, Lowe J, Kovoor A, ''et al.'' |title=Threonine 180 is required for G-protein-coupled receptor kinase 3- and beta-arrestin 2-mediated desensitization of the mu-opioid receptor in Xenopus oocytes. |journal=J. Biol. Chem. |volume=276 |issue= 7 |pages= 4894-900 |year= 2001 |pmid= 11060299 |doi= 10.1074/jbc.M007437200 }}
*{{cite journal  | author=Blaukat A |title=Determination of bradykinin B2 receptor in vivo phosphorylation sites and their role in receptor function |journal=J. Biol. Chem. |volume=276 |issue= 44 |pages= 40431–40 |year= 2001 |pmid= 11517230 |doi= 10.1074/jbc.M107024200  |name-list-format=vanc| author2=Pizard A | author3=Breit A  | display-authors=3  | last4=Wernstedt  | first4=C  | last5=Alhenc-Gelas  | first5=F  | last6=Muller-Esterl  | first6=W  | last7=Dikic  | first7=I }}
*{{cite journal | author=Blaukat A, Pizard A, Breit A, ''et al.'' |title=Determination of bradykinin B2 receptor in vivo phosphorylation sites and their role in receptor function. |journal=J. Biol. Chem. |volume=276 |issue= 44 |pages= 40431-40 |year= 2001 |pmid= 11517230 |doi= 10.1074/jbc.M107024200 }}
*{{cite journal  | author=Wang J |title=Role of tyrosine phosphorylation in ligand-independent sequestration of CXCR4 in human primary monocytes-macrophages |journal=J. Biol. Chem. |volume=276 |issue= 52 |pages= 49236–43 |year= 2002 |pmid= 11668182 |doi= 10.1074/jbc.M108523200  |name-list-format=vanc| author2=Guan E  | author3=Roderiquez G  | display-authors=3  | last4=Calvert  | first4=V  | last5=Alvarez  | first5=R  | last6=Norcross  | first6=MA }}
*{{cite journal  | author=Wang J, Guan E, Roderiquez G, ''et al.'' |title=Role of tyrosine phosphorylation in ligand-independent sequestration of CXCR4 in human primary monocytes-macrophages. |journal=J. Biol. Chem. |volume=276 |issue= 52 |pages= 49236-43 |year= 2002 |pmid= 11668182 |doi= 10.1074/jbc.M108523200 }}
*{{cite journal  | author=Obara K |title=G-protein coupled receptor kinase 2 and 3 expression in human detrusor cultured smooth muscle cells |journal=Urol. Res. |volume=29 |issue= 5 |pages= 325–9 |year= 2002 |pmid= 11762794 |doi=10.1007/s002400100207  |name-list-format=vanc| author2=Arai K | author3=Tomita Y  | display-authors=3  | last4=Hatano  | first4=Akihiko  | last5=Takahashi  | first5=Kota  }}
*{{cite journal  | author=Obara K, Arai K, Tomita Y, ''et al.'' |title=G-protein coupled receptor kinase 2 and 3 expression in human detrusor cultured smooth muscle cells. |journal=Urol. Res. |volume=29 |issue= 5 |pages= 325-9 |year= 2002 |pmid= 11762794 |doi=  }}
*{{cite journal  | vauthors=Mandyam CD, Thakker DR, Christensen JL, Standifer KM |title=Orphanin FQ/nociceptin-mediated desensitization of opioid receptor-like 1 receptor and mu opioid receptors involves protein kinase C: a molecular mechanism for heterologous cross-talk |journal=J. Pharmacol. Exp. Ther. |volume=302 |issue= 2 |pages= 502–9 |year= 2002 |pmid= 12130708 |doi= 10.1124/jpet.102.033159 }}
*{{cite journal | author=Mandyam CD, Thakker DR, Christensen JL, Standifer KM |title=Orphanin FQ/nociceptin-mediated desensitization of opioid receptor-like 1 receptor and mu opioid receptors involves protein kinase C: a molecular mechanism for heterologous cross-talk. |journal=J. Pharmacol. Exp. Ther. |volume=302 |issue= 2 |pages= 502-9 |year= 2002 |pmid= 12130708 |doi= 10.1124/jpet.102.033159 }}
*{{cite journal  | author=Strausberg RL |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241  |name-list-format=vanc| author2=Feingold EA  | author3=Grouse LH  | display-authors=3  | last4=Derge  | first4=JG  | last5=Klausner  | first5=RD  | last6=Collins  | first6=FS  | last7=Wagner  | first7=L  | last8=Shenmen  | first8=CM  | last9=Schuler  | first9=GD }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal | author=Barrett TB |title=Evidence that a single nucleotide polymorphism in the promoter of the G protein receptor kinase 3 gene is associated with bipolar disorder |journal=Mol. Psychiatry |volume=8 |issue= 5 |pages= 546–57 |year= 2004 |pmid= 12808434 |doi= 10.1038/sj.mp.4001268  |name-list-format=vanc| author2=Hauger RL  | author3=Kennedy JL  | display-authors=3  | last4=Sadovnick  | first4=A D  | last5=Remick  | first5=R A  | last6=Keck  | first6=P E  | last7=McElroy  | first7=S L  | last8=Alexander  | first8=M  | last9=Shaw  | first9=S H }}
*{{cite journal  | author=Barrett TB, Hauger RL, Kennedy JL, ''et al.'' |title=Evidence that a single nucleotide polymorphism in the promoter of the G protein receptor kinase 3 gene is associated with bipolar disorder. |journal=Mol. Psychiatry |volume=8 |issue= 5 |pages= 546-57 |year= 2004 |pmid= 12808434 |doi= 10.1038/sj.mp.4001268 }}
*{{cite journal  | author=Ota T |title=Complete sequencing and characterization of 21,243 full-length human cDNAs |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285  |name-list-format=vanc| author2=Suzuki Y  | author3=Nishikawa T  | display-authors=3  | last4=Otsuki  | first4=Tetsuji  | last5=Sugiyama  | first5=Tomoyasu  | last6=Irie  | first6=Ryotaro  | last7=Wakamatsu  | first7=Ai  | last8=Hayashi  | first8=Koji  | last9=Sato  | first9=Hiroyuki }}
*{{cite journal  | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal  | vauthors=Dzimiri N, Muiya P, Andres E, Al-Halees Z |title=Differential functional expression of human myocardial G protein receptor kinases in left ventricular cardiac diseases |journal=Eur. J. Pharmacol. |volume=489 |issue= 3 |pages= 167–77 |year= 2005 |pmid= 15087239 |doi= 10.1016/j.ejphar.2004.03.015 }}
*{{cite journal  | author=Dzimiri N, Muiya P, Andres E, Al-Halees Z |title=Differential functional expression of human myocardial G protein receptor kinases in left ventricular cardiac diseases. |journal=Eur. J. Pharmacol. |volume=489 |issue= 3 |pages= 167-77 |year= 2005 |pmid= 15087239 |doi= 10.1016/j.ejphar.2004.03.015 }}
*{{cite journal  | author=Teli T |title=Regulation of corticotropin-releasing hormone receptor type 1alpha signaling: structural determinants for G protein-coupled receptor kinase-mediated phosphorylation and agonist-mediated desensitization |journal=Mol. Endocrinol. |volume=19 |issue= 2 |pages= 474–90 |year= 2005 |pmid= 15498832 |doi= 10.1210/me.2004-0275  |name-list-format=vanc| author2=Markovic D  | author3=Levine MA  | display-authors=3  | last4=Hillhouse  | first4=EW  | last5=Grammatopoulos  | first5=DK }}
*{{cite journal | author=Teli T, Markovic D, Levine MA, ''et al.'' |title=Regulation of corticotropin-releasing hormone receptor type 1alpha signaling: structural determinants for G protein-coupled receptor kinase-mediated phosphorylation and agonist-mediated desensitization. |journal=Mol. Endocrinol. |volume=19 |issue= 2 |pages= 474-90 |year= 2005 |pmid= 15498832 |doi= 10.1210/me.2004-0275 }}
*{{cite journal  | author=Feng YH |title=ATP stimulates GRK-3 phosphorylation and β-arrestin-2-dependent internalization of P2X7 receptor |journal=Am. J. Physiol., Cell Physiol. |volume=288 |issue= 6 |pages= C1342–56 |year= 2005 |pmid= 15728711 |doi= 10.1152/ajpcell.00315.2004  | pmc=2598767  |name-list-format=vanc| author2=Wang L  | author3=Wang Q  | display-authors=3  | last4=Li  | first4=X  | last5=Zeng  | first5=R  | last6=Gorodeski  | first6=GI }}
*{{cite journal  | author=Feng YH, Wang L, Wang Q, ''et al.'' |title=ATP stimulates GRK-3 phosphorylation and beta-arrestin-2-dependent internalization of P2X7 receptor. |journal=Am. J. Physiol., Cell Physiol. |volume=288 |issue= 6 |pages= C1342-56 |year= 2005 |pmid= 15728711 |doi= 10.1152/ajpcell.00315.2004 }}
*{{cite journal  | author=Rual JF |title=Towards a proteome-scale map of the human protein-protein interaction network |journal=Nature |volume=437 |issue= 7062 |pages= 1173–8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209  |name-list-format=vanc| author2=Venkatesan K  | author3=Hao T  | display-authors=3  | last4=Hirozane-Kishikawa  | first4=Tomoko  | last5=Dricot  | first5=Amélie  | last6=Li  | first6=Ning  | last7=Berriz  | first7=Gabriel F.  | last8=Gibbons  | first8=Francis D.  | last9=Dreze  | first9=Matija }}
*{{cite journal | author=Rual JF, Venkatesan K, Hao T, ''et al.'' |title=Towards a proteome-scale map of the human protein-protein interaction network. |journal=Nature |volume=437 |issue= 7062 |pages= 1173-8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 }}
}}
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== External links ==
== External links ==
* [http://www.nature.com/cgi-taf/DynaPage.taf?file=/mp/journal/v8/n5/abs/4001268a.html&dynoptions=doi1056040331 Online version of the paper in ''Molecular Psychiatry'']
* [http://www.nature.com/cgi-taf/DynaPage.taf?file=/mp/journal/v8/n5/abs/4001268a.html&dynoptions=doi1056040331 Online version of the paper in ''Molecular Psychiatry'']
* [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12808434&dopt=Abstract PubMed abstract]
* [https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12808434&dopt=Abstract PubMed abstract]
* [http://www.sciencedaily.com/releases/2003/06/030617080403.htm Report from sciencedaily.com]
* [http://www.sciencedaily.com/releases/2003/06/030617080403.htm Report from sciencedaily.com]
* {{UCSC gene info|ADRBK2}}
{{Serine/threonine-specific protein kinases}}
{{Enzymes}}
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[[Category:Genes]]
{{DEFAULTSORT:Beta Adrenergic Receptor Kinase-2}}
{{genetics-stub}}
[[Category:Human genes]]
{{disease-stub}}
[[Category:Biology of bipolar disorder]]
[[Category:EC 2.7.11]]

Revision as of 04:55, 30 August 2017

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Beta-adrenergic receptor kinase 2 (beta-ARK-2) also known as G-protein-coupled receptor kinase 3 (GRK3) is an enzyme that in humans is encoded by the ADRBK2 gene.[1][2]

Function

The beta-adrenergic receptor kinase specifically phosphorylates the agonist-occupied form of the beta-adrenergic and related G protein-coupled receptors. Overall, the beta adrenergic receptor kinase 2 has 85% amino acid similarity with beta adrenergic receptor kinase 1, with the protein kinase catalytic domain having 95% similarity. These data suggest the existence of a family of receptor kinases which may serve broadly to regulate receptor function.[2]

Discovery

The beta adrenergic receptor kinase-2 was cloned from mice and rats in 1991[3] and the human gene was cloned in 1993.[4]

Clinical significance

Gene linkage techniques were used to identify a mutation in the GRK3 gene as a possible cause of up to 10% of cases of bipolar disorder.[5] Beta adrenergic receptor kinase-2 appears to affect dopamine metabolism. Subsequent studies, while noting that chromosome 22q12 may harbor a risk gene for schizophrenia, did not find that the gene coding for beta adrenergic receptor kinase-2 was linked to schizophrenia.[6]

It has been associated with WHIM syndrome.[7]

References

  1. ↑ Calabrese G, Sallese M, Stornaiuolo A, Stuppia L, Palka G, De Blasi A (Feb 1995). "Chromosome mapping of the human arrestin (SAG), beta-arrestin 2 (ARRB2), and beta-adrenergic receptor kinase 2 (ADRBK2) genes". Genomics. 23 (1): 286–8. doi:10.1006/geno.1994.1497. PMID 7695743.
  2. ↑ 2.0 2.1 "Entrez Gene: ADRBK2 adrenergic, beta, receptor kinase 2".
  3. ↑ Benovic JL, Onorato JJ, Arriza JL, Stone WC, Lohse M, Jenkins NA, Gilbert DJ, Copeland NG, Caron MG, Lefkowitz RJ (August 1991). "Cloning, expression, and chromosomal localization of beta-adrenergic receptor kinase 2. A new member of the receptor kinase family". J. Biol. Chem. 266 (23): 14939–46. PMID 1869533.
  4. ↑ Parruti G, Ambrosini G, Sallese M, De Blasi A (January 1993). "Molecular cloning, functional expression and mRNA analysis of human beta-adrenergic receptor kinase 2". Biochem. Biophys. Res. Commun. 190 (2): 475–81. doi:10.1006/bbrc.1993.1072. PMID 8427589.
  5. ↑ Barrett TB, Hauger RL, Kennedy JL, Sadovnick AD, Remick RA, Keck PE, McElroy SL, Alexander M, Shaw SH, Kelsoe JR (May 2003). "Evidence that a single nucleotide polymorphism in the promoter of the G protein receptor kinase 3 gene is associated with bipolar disorder". Mol. Psychiatry. 8 (5): 546–57. doi:10.1038/sj.mp.4001268. PMID 12808434.
  6. ↑ Yu SY, Takahashi S, Arinami T, Ohkubo T, Nemoto Y, Tanabe E, Fukura Y, Matsuura M, Han YH, Zhou RL, Shen YC, Matsushima E, Kojima T (February 2004). "Mutation screening and association study of the beta-adrenergic receptor kinase 2 gene in schizophrenia families". Psychiatry Res. 125 (2): 95–104. doi:10.1016/j.psychres.2003.12.003. PMID 15006433.
  7. ↑ Balabanian K, Levoye A, Klemm L, et al. (March 2008). "Leukocyte analysis from WHIM syndrome patients reveals a pivotal role for GRK3 in CXCR4 signaling". J. Clin. Invest. 118 (3): 1074–84. doi:10.1172/JCI33187. PMC 2242619. PMID 18274673.

Further reading

External links

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