PKR<sub>2</sub> | Prokineticin receptors | IUPHAR/BPS Guide to PHARMACOLOGY

PKR2

Target id: 336

Nomenclature: PKR2

Family: Prokineticin receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for PKR2 in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 384 20p12.3 PROKR2 prokineticin receptor 2 22,44
Mouse 7 381 2 F2 Prokr2 prokineticin receptor 2 10
Rat 7 383 4q34 Prokr2 prokineticin receptor 2 25,31
Previous and Unofficial Names
GPR73b [22] | VEGFR-2 [21] | GPR73a [22] | GPRg2 [44] | I5E [25]
Database Links
Specialist databases
GPCRDB pkr2_human (Hs), pkr2_mouse (Mm), pkr2_rat (Rn)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
prokineticin-1 {Sp: Human}
prokineticin-2 {Sp: Human}
prokineticin-1 {Sp: Mouse}
prokineticin-2 {Sp: Mouse, Rat}
prokineticin-1 {Sp: Rat}
Comments: Prokineticin-2 is the higher potency endogenous agonist
Potency order of endogenous ligands (Human)
prokineticin-2 (PROK2, Q9HC23) > prokineticin-1 (PROK1, Q9HC23) > prokineticin-2β (PROK2)  [22,25,44]

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
MIT1 Hs Full agonist 9.2 pIC50 25
pIC50 9.2 [25]
[125I]BH-MIT1 Hs Agonist 9.2 pIC50 25
pIC50 9.2 (IC50 6.7x10-10 M) [25]
prokineticin-2 {Sp: Human} Hs Full agonist 8.1 – 8.2 pIC50 9,25
pIC50 8.1 – 8.2 [9,25]
prokineticin-1 {Sp: Human} Hs Full agonist 7.1 – 7.3 pIC50 9,25
pIC50 7.1 – 7.3 [9,25]
prokineticin-2β {Sp: Human} Hs Full agonist <6.0 pIC50 9
pIC50 <6.0 (IC50 >1x10-6 M) [9]
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
triazine compound PC1 Hs Antagonist 5.8 pKi 3
pKi 5.8 (Ki 1.61x10-6 M) [3]
PKR-A Hs Antagonist 7.3 – 7.4 pIC50 11
pIC50 7.3 – 7.4 (IC50 5.27x10-8 – 4.35x10-8 M) [11]
triazine compound PC10 Hs Antagonist 5.9 pIC50 18
pIC50 5.9 (IC50 1.2x10-6 M) [18]
Primary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
Comments:  Coexpression of Gqi5 with the PKR2 receptor increases the PK stimulated Ca2+ response in HEK 293 cells transfected with the human PKR2 receptor [9].
References:  9,28
Secondary Transduction Mechanisms
Transducer Effector/Response
Gs family
Gi/Go family
Adenylate cyclase stimulation
Other - See Comments
Comments:  Pertussis toxin (PTX) inhibits PK1-induced mitogen-activated protein kinase signaling suggesting that PKR2 couples to Gi/Go proteins [23].
References:  9,23
Tissue Distribution
Brain, testis, small intestine.
Species:  Human
Technique:  RT-PCR.
References:  22
Testis.
Species:  Human
Technique:  RT-PCR.
References:  44
Endocrine tissues: ovary, thyroid gland, salivary gland, pituitary gland.
Species:  Human
Technique:  RT-PCR.
References:  22
Capillary endothelial cells of the testis interstitium.
Species:  Human
Technique:  in situ hybridisation.
References:  20
CNS: amygdala, hippocampus, frontal lobe, cerebral cortex, fetal brain.
Species:  Human
Technique:  RT-PCR.
References:  44
Endometrium.
Species:  Human
Technique:  RT-PCR.
References:  4
Brain >> mammary gland, spleen.
Species:  Human
Technique:  RT-PCR.
References:  9
Immune cells: CD19 >> CD14 > CD4, CD8, Th1, Th2.
Species:  Human
Technique:  Q-PCR.
References:  15
Capillary endothelial cells of the testis interstitium.
Species:  Mouse
Technique:  in situ hybridisation.
References:  20
Lymph node >> bone marrow.
Species:  Mouse
Technique:  Q-PCR.
References:  15
Macrophages.
Species:  Mouse
Technique:  RT-PCR.
References:  24
Brain, prostate, liver, testis, kidney.
Species:  Mouse
Technique:  Taqman analysis.
References:  19
Brain: suprachiasmatic nucleus (SCN), paraventricular thalamic nucleus (PVT), paraventricular hypothalamic nucleus (PVN), dorsal medial hypothalamic nucleus (DMH), paratenial thalamic nuclei (PT), paracentral thalamic nucleus (PC), lateral habenular nucleus (LHb), lateral septal nucleus (LS), lateral globus pallidus (LGP), amygdala.
Species:  Mouse
Technique:  in situ hybridisation.
References:  10
Testis > cerebrum, cerebellum, ovary, pituitary, lung, spleen, uterus.
Species:  Rat
Technique:  RT-PCR.
References:  25
Olfactory bulb: ependyma and subependymal layers of the olfactory ventricle, subventricular zone, rostral migratory stream.
Dentate gyrus of the hippocampus.
Species:  Rat
Technique: 
References:  32
Brain: piriform cortex, paraventricular thalamic nucleus (PVT), paratenial nucleus (PT), suprachiasmatic nucleus (SCN), hypothalamic paraventricular (PVH) and dorsomedial (DMH) nuclei, arcuate nucleus (ARC), subfornical organ (SFO), amygdala, hippocampus, lateral habenular nucleus and lateral globus pallidus.
Species:  Rat
Technique:  in situ hybridisation.
References:  30
Digestive tract: ileocecum.
Species:  Rat
Technique:  RT-PCR.
References:  22
CNS: dorsal root ganglia > dorsal quadrants of spinal cord.
Species:  Rat
Technique:  RT-PCR.
References:  31
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Measurement of intracellular [Ca2+] in CHO cells transfected with the human PKR2 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Mobilisation of Ca2+.
References:  5,15,22,44
Measurement of IP levels in COS-7 cells transfected with the human PKR2 receptor.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Increase in IP levels.
References:  22
Measurement of the activity of p44/p42 MAPK in HEK 293 cells transfected with the PKR2 receptor.
Species:  Human
Tissue:  HEK 293.
Response measured:  Phosphorylation of p44/p42 MAPK.
References:  22
Measurement of intracellular Ca2+ in CHO cells transfected with the rat PKR2 receptor.
Species:  Rat
Tissue:  CHO cells.
Response measured:  Increase in [Ca2+]i.
References:  25
Measurement of Ca2+ and cAMP levels in HEK 293 cells transfected with the human PKR2 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Mobilisation of Ca2+ and stimulation of cAMP accumulation.
References:  9
Physiological Functions
Regulation of behavioural circadian rhythm.
Species:  Rat
Tissue:  In vivo (suprachiasmatic nucleus).
References:  10
Proliferation, survival, and migration of adrenal cortical capillary endothelial (ACE) cells.
Species:  Mouse
Tissue:  Testis.
References:  20
Inhibition of food intake.
Species:  Rat
Tissue:  In vivo.
References:  30
Stimulation of water intake.
Species:  Rat
Tissue:  In vivo.
References:  30
Excitation (potential mechanism for circadian regulation).
Species:  Rat
Tissue:  subfornical organ neurons of the brain.
References:  13
Increase of the activity of acid-sensing ion channels.
Species:  Rat
Tissue:  Dorsal root ganglion
References:  37
Migration of neuroblasts.
Species:  Mouse
Tissue:  Subventricular zone (SVZ)
References:  36
Depolarization of hypothalamic paraventricular nucleus magnocellular and parvocellular neurons
Species:  Mouse
Tissue:  Brain
References:  50
Increase of the spontaneous firing rate and down-regulation of the function of GABAA receptor signaling.
Species:  Rat
Tissue:  Suprachiasmatic nucleus, trigeminal ganglion neurons
References:  39,49
Increase in the formation of caveolin clusters and vesicle trafficking in endothelial cells.
Species:  Mouse
Tissue:  Coronary endothelial cells
References:  17
Invasion of colon cancer cell lines.
Species:  Human
Tissue:  Colon cancer cells
References:  47
Physiological Consequences of Altering Gene Expression
Null mutation of Prokr2 disrupts circadian coordination of the activity cycle and thermoregulation.
Species:  Mouse
Tissue:  in vivo
Technique:  Gene knockouts
References:  35
Prokr2 deficient mice display abnormal development of the olfactory bulb and reproductive system, with similarities to the clinical features of Kallmann syndrome.
Species:  Mouse
Tissue:  in vivo
Technique:  Gene knockouts
References:  26
Prokr2 deficient mice display vascular dysmorphology of the fetal testes, with similarities to the clinical features of Kallmann syndrome.
Species:  Mouse
Tissue:  Testes
Technique:  Gene knockouts
References:  46
Prokr2 deficient mice present defective neuronal progenitor migration and differentiation, with similarities to the clinical features of Kallmann syndrome.
Species:  Mouse
Tissue:  Olfactory bulb, subventricular zone (SVZ)
Technique:  Gene knockouts
References:  34
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0003651 abnormal axon outgrowth PMID: 16537498 
Prokr2tm1Brd Prokr2tm1Brd/Prokr2tm1Brd
involves: 129S7/SvEvBrd * C57BL/6
MGI:2181363  MP:0001777 abnormal body temperature regulation PMID: 17202262 
Prokr2tm1Brd Prokr2tm1Brd/Prokr2tm1Brd
involves: 129S7/SvEvBrd * C57BL/6
MGI:2181363  MP:0002561 abnormal circadian phase PMID: 17202262 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0001119 abnormal female reproductive system morphology PMID: 16537498 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0005645 abnormal hypothalamus physiology PMID: 16537498 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0001145 abnormal male reproductive system morphology PMID: 16537498 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0000627 abnormal mammary gland morphology PMID: 16537498 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0002882 abnormal neuron morphology PMID: 16537498 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0002739 abnormal olfactory bulb development PMID: 16537498 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0000819 abnormal olfactory bulb morphology PMID: 16537498 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0002216 abnormal seminiferous tubule morphology PMID: 16537498 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0001134 absent corpus luteum PMID: 16537498 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0008261 arrest of male meiosis PMID: 16537498 
Prokr2tm1Brd Prokr2tm1Brd/Prokr2tm1Brd
involves: 129S7/SvEvBrd * C57BL/6
MGI:2181363  MP:0002560 arrhythmic circadian persistence PMID: 17202262 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0005159 azoospermia PMID: 16537498 
Prokr2tm1Brd Prokr2tm1Brd/Prokr2tm1Brd
involves: 129S7/SvEvBrd * C57BL/6
MGI:2181363  MP:0005534 decreased body temperature PMID: 17202262 
Prokr2tm1Brd Prokr2tm1Brd/Prokr2tm1Brd
B6.129S7-Prokr2
MGI:2181363  MP:0001262 decreased body weight PMID: 17202262 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0002780 decreased circulating testosterone level PMID: 16537498 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0005130 decreased follicle stimulating hormone level PMID: 16537498 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0002682 decreased mature ovarian follicle number PMID: 16537498 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0004856 decreased ovary weight PMID: 16537498 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0004852 decreased testis weight PMID: 16537498 
Prokr2tm1Brd Prokr2tm1Brd/Prokr2tm1Brd
involves: 129S7/SvEvBrd * C57BL/6
MGI:2181363  MP:0001402 hypoactivity PMID: 17202262 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0005536 Leydig cell hypoplasia PMID: 16537498 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0002058 neonatal lethality PMID: 16537498 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0004833 ovary atrophy PMID: 16537498 
Prokr2tm1Brd Prokr2tm1Brd/Prokr2tm1Brd
B6.129S7-Prokr2
MGI:2181363  MP:0002082 postnatal lethality PMID: 17202262 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0002741 small olfactory bulb PMID: 16537498 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0001153 small seminiferous tubules PMID: 16537498 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0003205 testicular atrophy PMID: 16537498 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0004894 uterus atrophy PMID: 16537498 
Prokr2tm1Api Prokr2tm1Api/Prokr2tm1Api
involves: C57BL/6 * CBA
MGI:2181363  MP:0004895 vagina atrophy PMID: 16537498 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Anosmia, isolated congenital; ANIC
Synonyms: Congenital anosmia [Disease Ontology: DOID:0050333]
Disease Ontology: DOID:0050333
OMIM: 107200
Orphanet: ORPHA88620
References:  29
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human R85C 29
Missense Human R85H 29
Missense Human P290S 29
Disease:  Hirschsprung disease
OMIM: 142623
Orphanet: ORPHA388
References:  41
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human G68S 41
Missense Human R85C 41
Missense Human R85H 41
Missense Human P290S 41
Missense Human V297I 41
Disease:  Hypogonadotropic hypogonadism 3 with or without anosmia; HH3
Synonyms: Kallmann syndrome [Orphanet: ORPHA478] [Disease Ontology: DOID:3614]
Disease Ontology: DOID:3614
OMIM: 244200
Orphanet: ORPHA478
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human A51T No functional consequence detected
Missense Human R80C No functional consequence detected 1-2
Missense Human R85C Substitution results in a mild G protein-coupling defect 1,28
Missense Human R85H Substitution results in a mild G protein-coupling defect 1,14,28
Missense Human R85L Substitution results in a cell surface-targeting defect 42
Missense Human Y113H Substitution results in a cell surface-targeting defect 12
Missense Human V115M Substitution results in a cell surface-targeting defect 12
Missense Human R117W Substitution results in a cell surface-targeting defect
Missense Human R164Q Substitution results in a mild G protein-coupling defect 12,14,28
Missense Human L173R Substitution results in a cell surface-targeting defect 2,6,12,14,28
Missense Human W178S Substitution results in a cell surface-targeting defect 14,28
Missense Human S188L Substitution results in a cell surface-targeting defect
Missense Human Q210R Substitution affects ligand binding 14,28
Missense Human G234D Substitution results in a cell surface-targeting defec 48
Missense Human W251L Substitution results in a cell surface-targeting defect 42
Missense Human R268C No functional consequence detected 2,28
Missense Human V274D Substitution results in a cell surface-targeting defect 43
Missense Human P290S Substitution results in a cell surface-targeting defect 14,28
Missense Human M323I No functional consequence detected 14,28
Missense Human V331M Substitution results in a mild G protein-coupling defect 12,14,28
Missense Human R357W No functional consequence detected 12
Nonsense Human Y140X mRNA decay or protein truncation 2
Disease:  Hypopituitarism with pituitary stalk interruption
References:  27,40
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human A51T 27,40
Missense Human R85L 27
Missense Human R85H 40
Missense Human L173R 27,40
Missense Human R268C 27
Missense Human G371R 27
Disease:  Hypothalamic amenorrhea
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human R85H 7
Missense Human L173R 7
Disease:  Idiopathic hypogonadotropic hypogonadism
Role: 
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human V317L 16
Disease:  Normosmic congenital hypogonadotropic hypogonadism
Orphanet: ORPHA432
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human R85C 12
Missense Human W178S 12
Missense Human S188L 12
Missense Human S202G 8
Missense Human R248Q 12
Missense Human R268C 2
Disease:  Septo-optic dysplasia
OMIM: 182230
Orphanet: ORPHA3157
References:  27,38
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human A51T 27
Missense Human R85G 38
Missense Human R173R 27
Missense Human R268C 27,38
Missense Human G371R 27
Clinically-Relevant Mutations and Pathophysiology Comments
Mutations found in the homozygous state: Kallmann syndrome (R85C, R85H, Y140X, R164Q, L173R, V274D, P290S, G234D, R268C). For other possible variants of PKR2 due to single nucleotide polymorphism (SNP) see reference [45] and the Exome Variant Server Data Browser.
Biologically Significant Variants
Type:  Missense mutation
Species:  Human
Description:  V331M substitution results in a mild G protein-coupling defect and is associated with Kallmann syndrome and is reported to confer protective roles in early pregnancy.
Amino acid change:  V331M
SNP accession: 
References:  12,14,28,45
Biologically Significant Variant Comments
In most cases, only one allele is affected by the mutation. In heterozygotes the two main clinical features of Kallmann syndrome may be incomplete. Several phenotypes are possible for individuals harboring only one mutant allele:
(1) no symptoms, with normal olfaction and complete pubertal development
(2) congenital isolated (idiopathic) hypogonadotropic hypogonadism (IHH) but normal olfaction
(3) anosmia/hyposmia but normal pubertal development and gonadal function
(4) the two cardinal clinical Kallmann syndrome signs, anosmia and IHH.
These phenotypic dissociations can be seen in family members with the same PROKR2 mutations. By contrast, patients with two mutant alleles almost always have the cardinal signs of Kallmann syndrome.

Other mutations in PROKR2 associated with cancer [33] (*, stop codon; fs, frameshift)
carcinoma:
lung: D38N, R47W, K53N, K83N, D99N, W121*, I174N, A175S, P213H, E231D
ovary: R85C, L95P, R298C, R353H
breast: S23F, G293S, M341I
liver L95P, I184fs*56
rectum C242*, R368I
larynx D112Y, C279S
pharynx R268G
prostate Y220*
kidney: G124C
endometrium: V115M
colon: A322T
melanoma: E110K, R298C
neuroblastoma: F109L
glioma: M165I
others:
pancreas: A77T, V331M

References

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1. Abreu AP, Noel SD, Xu S, Carroll RS, Latronico AC, Kaiser UB. (2012) Evidence of the importance of the first intracellular loop of prokineticin receptor 2 in receptor function. Mol. Endocrinol., 26 (8): 1417-27. [PMID:22745195]

2. Abreu AP, Trarbach EB, de Castro M, Frade Costa EM, Versiani B, Matias Baptista MT, Garmes HM, Mendonca BB, Latronico AC. (2008) Loss-of-function mutations in the genes encoding prokineticin-2 or prokineticin receptor-2 cause autosomal recessive Kallmann syndrome. J. Clin. Endocrinol. Metab., 93 (10): 4113-8. [PMID:18682503]

3. Balboni G, Lazzari I, Trapella C, Negri L, Lattanzi R, Giannini E, Nicotra A, Melchiorri P, Visentin S, Nuccio CD et al.. (2008) Triazine compounds as antagonists at Bv8-prokineticin receptors. J. Med. Chem., 51 (23): 7635-9. [PMID:19006379]

4. Battersby S, Critchley HO, Morgan K, Millar RP, Jabbour HN. (2004) Expression and regulation of the prokineticins (endocrine gland-derived vascular endothelial growth factor and Bv8) and their receptors in the human endometrium across the menstrual cycle. J Clin Endocrinol Metab, 89: 6463-6469. [PMID:15126578]

5. Bullock CM, Li JD, Zhou QY. (2004) Structural determinants required for the bioactivities of prokineticins and identification of prokineticin receptor antagonists. Mol Pharmacol, 65: 582-588. [PMID:14978236]

6. Canto P, Munguía P, Söderlund D, Castro JJ, Méndez JP. (2009) Genetic analysis in patients with Kallmann syndrome: coexistence of mutations in prokineticin receptor 2 and KAL1. J. Androl., 30 (1): 41-5. [PMID:18723471]

7. Caronia LM, Martin C, Welt CK, Sykiotis GP, Quinton R, Thambundit A, Avbelj M, Dhruvakumar S, Plummer L, Hughes VA et al.. (2011) A genetic basis for functional hypothalamic amenorrhea. N. Engl. J. Med., 364 (3): 215-25. [PMID:21247312]

8. Chan YM, de Guillebon A, Lang-Muritano M, Plummer L, Cerrato F, Tsiaras S, Gaspert A, Lavoie HB, Wu CH, Crowley Jr WF et al.. (2009) GNRH1 mutations in patients with idiopathic hypogonadotropic hypogonadism. Proc. Natl. Acad. Sci. U.S.A., 106 (28): 11703-8. [PMID:19567835]

9. Chen J, Kuei C, Sutton S, Wilson S, Yu J, Kamme F, Mazur C, Lovenberg T, Liu C. (2005) Identification and pharmacological characterization of prokineticin 2 beta as a selective ligand for prokineticin receptor 1. Mol Pharmacol, 67: 2070-2076. [PMID:15772293]

10. Cheng MY, Bullock CM, Li C, Lee AG, Bermak JC, Belluzzi J, Weaver DR, Leslie FM, Zhou QY. (2002) Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus. Nature, 417: 405-410. [PMID:12024206]

11. Cheng MY, Lee AG, Culbertson C, Sun G, Talati RK, Manley NC, Li X, Zhao H, Lyons DM, Zhou QY et al.. (2012) Prokineticin 2 is an endangering mediator of cerebral ischemic injury. Proc. Natl. Acad. Sci. U.S.A., 109 (14): 5475-80. [PMID:22431614]

12. Cole LW, Sidis Y, Zhang C, Quinton R, Plummer L, Pignatelli D, Hughes VA, Dwyer AA, Raivio T, Hayes FJ et al.. (2008) Mutations in prokineticin 2 and prokineticin receptor 2 genes in human gonadotrophin-releasing hormone deficiency: molecular genetics and clinical spectrum. J. Clin. Endocrinol. Metab., 93 (9): 3551-9. [PMID:18559922]

13. Cottrell GT, Zhou QY, Ferguson AV. (2004) Prokineticin 2 modulates the excitability of subfornical organ neurons. J Neurosci, 24: 2375-2379. [PMID:15014112]

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Philippe Rondard, Oualid Sbai.
Prokineticin receptors: PKR2. Last modified on 13/07/2018. Accessed on 15/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=336.