CALCIUM SIGNALING PATHWAY VIA THE CALCIUM-SENSING RECEPTOR (PW:0001141) Description
Calcium (Ca2+) signaling via the calcium-sensing receptor (Casr) exerts important roles in calcium homeostasis; it inhibits the secretion of parathyroid hormone (PTH) in parathyroid glands and regulates calcium absorption and water balance in the kidney, the two tissues where the receptor is most abundantly expressed. The function of Casr is also important for the proper functioning of cells involved in bone remodeling and of many types of neural cells, among others. In addition to Ca2+, the receptor binds a number of agonists or 'calcimimetics' of which those that activate the receptor independent of Ca2+ are referred to as type I or orthosteric agonists while those that require the metal ion acting as positive allosteric modulators (PAMs) are known as type II calcimimetics. At the other end of the spectrum are the 'calcilytics' or the negative modulators (NAMs) of Casr. The receptor is a G-protein coupled receptor (GPCR) that belongs to the C group. Discovered in early 90s, it is believed to have evolved from a common ancestor that belonged to the bacterial nutrient periplasmic binding protein family. A feature of the large extracellular domain characteristic of group C proteins is the presence of the Venus flytrap (VFT) module with which the bacterial proteins share sequence similarity. The VFTM is a bi-lobed structure with a crevice in between involved in ligand recognition and undergoing conformational changes upon its binding. Residues critical for Ca2+ binding are within the crevice with two additional sites discovered, one in each lobe. Overall, the receptor binds cooperatively 3 to 5 metal ions. The extracellular domain is also the site of several cysteine residues, some of which have been shown to be important for the covalent disulfide bond of the obligate Casr dimer. Of note is that Casr can also heterodimerize with other C group GPCRs. Calcimimetics and calcilytics bind to/within the transmembrane domain to overlapping, but not identical sites. Casr exerts pleiotropic effects by engaging several alpha subunit types of heterotrimeric G proteins; its downstream signaling is complex and cell specific but many of its molecular underpinnings remain to be determined. CasR activates Galphai leading to inhibition of adenylyl cyclases and reduced production of cAMP. Activation of Galphaq type and subsequent activation of phospholipase C, leads to production of diacylglycerol (DAG) and activation of PKC signaling and to production of inositol 1,4,5-triphosphate (IP3) and subsequent release of Ca2+ from intracellular stores. PKC is believed to provide a negative regulatory loop as Casr activated PKC may in turn phosphorylate and inhibit the receptor which contains several putative PKC binding sites. Casr may also activate the Galpha12/13 pathway. Note that Casr switches from Galphai coupling in normal mammary epithelial cells to Galphas in breast cancer cell lines. Downstream MAPK pathways are triggered in response to Casr activation, particularly the one mediated by Erk1/2; results support the view that both Galphaq and Galphai pathways are involved. The monomeric G protein Rho/Rac/Cdc42 pathway is also activated downstream of either Galphaq or Galpha12/13, depending on the system. Filamin A (Flna) binds to the intracellular tail of Casr and is believed to act as a scaffold coupling Galpha subunits and RhoA (a complex of Casr, RhoA, flna and Lbc (a guanyl-nucleotide exchange factor (GEF) for Rho) can be immunoprecipitated). Several other interacting partners have been identified but their functional relevance remains to be established (selected partners are listed in the accompanying link, but they are not annotated to the term). The G-protein coupled kinases (GRKs) and beta-arrestins partners are known components of GPCRs mediated pathways: GRKs phosphorylate the activated receptor which is then recognized by beta-arrestins whose binding precludes the association of the receptor with G proteins (receptor desensitization). Beta-arrestins have been shown to promote activation of Erk1/2 pathway downstream of Casr . The regulators of G protein signaling (RGS) proteins act as GTP activating proteins (GAP) that accelerate GTP hydrolysis resulting in inactivation of the Galpha subunit and termination of signaling: several inhibit Casr mediated signaling. Loss-of-function or inactivating as well as activating, gain-of function mutations have been identified; many but not all are located in the extracellular domain of the receptor. Additional information can be found at
the CaSR database .
To see the ontology report for annotations, Gviewer and download, click here .
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Pathway Diagram:
GO TO:
Genes in Pathway:
Symbol
Object Name
Evidence
Notes
Source
PubMed Reference(s)
RGD Reference(s)
Position
G
Arrb1
arrestin, beta 1
ISO IMP
RGD
PMID:15637145 PMID:22192592
RGD:7207060 , RGD:7207059
NCBI chr 1:163,249,654...163,321,711
Ensembl chr 1:153,838,078...153,904,061
G
Arrb2
arrestin, beta 2
ISO IMP
RGD
PMID:15637145 PMID:22192592
RGD:7207060 , RGD:7207059
NCBI chr10:55,645,539...55,653,485
Ensembl chr10:55,146,818...55,154,850
G
Casr
calcium-sensing receptor
IMP IDA
RGD
PMID:22192592 PMID:15637145 PMID:12239094
RGD:7207059 , RGD:7207060 , RGD:7207227
NCBI chr11:77,738,398...77,813,639
Ensembl chr11:64,235,251...64,304,811
G
Flna
filamin A
ISO
RGD
PMID:12239094
RGD:7207227
NCBI chr X:157,159,051...157,185,559
Ensembl chr X:152,007,758...152,031,052
G
Grk2
G protein-coupled receptor kinase 2
ISO
RGD
PMID:15637145
RGD:7207060
NCBI chr 1:211,010,259...211,031,013
Ensembl chr 1:201,581,480...201,601,582
G
Grk3
G protein-coupled receptor kinase 3
ISO
RGD
PMID:15637145
RGD:7207060
NCBI chr12:43,624,778...43,735,375
Ensembl chr12:43,624,897...43,731,262
G
Grk4
G protein-coupled receptor kinase 4
ISO
RGD
PMID:15637145
RGD:7207060
NCBI chr14:75,998,554...76,080,808
Ensembl chr14:76,006,218...76,080,693
G
Rgs12
regulator of G-protein signaling 12
ISO
RGD
PMID:12239094
RGD:7207227
NCBI chr14:75,715,925...75,824,012
Ensembl chr14:75,715,934...75,794,596
G
Rgs2
regulator of G-protein signaling 2
ISO
RGD
PMID:12239094
RGD:7207227
NCBI chr13:55,799,749...55,802,354
Ensembl chr13:55,798,829...55,802,385
G
Rgs4
regulator of G-protein signaling 4
ISO
RGD
PMID:12239094
RGD:7207227
NCBI chr13:84,469,593...84,475,884
Ensembl chr13:81,936,775...81,943,068
G
Rgs5
regulator of G-protein signaling 5
ISO
RGD
PMID:21393447
RGD:7207228
NCBI chr13:84,381,077...84,417,875
Ensembl chr13:81,836,304...81,885,518
G
Rhoa
ras homolog family member A
ISO
RGD
PMID:12239094
RGD:7207227
NCBI chr 8:117,870,548...117,904,303
Ensembl chr 8:108,991,954...109,025,746
Additional Elements in Pathway: (includes Gene Groups, Small Molecules, Other Pathways..etc.)
Pathway Gene Annotations
Disease Annotations Associated with Genes in the calcium signaling pathway via the calcium-sensing receptor
Arrb1 3-methylglutaconic aciduria type 7b , Arteriovenous Fistula , colitis , congestive heart failure , Experimental Arthritis , intellectual disability , liver cirrhosis , major depressive disorder , Transplant Rejection Arrb2 alcohol dependence , amphetamine abuse , Arteriovenous Fistula , brain infarction , drug psychosis , Experimental Arthritis , Experimental Liver Cirrhosis , Experimental Liver Neoplasms , glioblastoma , hepatocellular carcinoma , heroin dependence , hypertension , liver cirrhosis , metabolic dysfunction and alcohol associated liver disease , Myocardial Reperfusion Injury , nicotine dependence , opiate dependence , pain agnosia , portal hypertension , renal fibrosis , Transplant Rejection , type 2 diabetes mellitus Casr Albuminuria , alkaptonuria , atherosclerosis , autosomal dominant hypocalcemia , autosomal dominant hypocalcemia 1 , Autosomal Dominant Hypocalcemia, with Bartter Syndrome , Bartter disease type 3 , breast cancer , calcium oxalate nephrolithiasis , cardiomyopathy , Developmental Disabilities , Diabetic Cardiomyopathies , end stage renal disease , Experimental Diabetes Mellitus , familial hypocalciuric hypercalcemia , familial hypocalciuric hypercalcemia 1 , familial isolated hypoparathyroidism , genetic disease , Gitelman syndrome , Hereditary Neoplastic Syndromes , hypercalcemia , Hypercalciuria , hyperparathyroidism , Hyperparathyroidism, Neonatal Severe Primary , hypertrophic cardiomyopathy , Hypocalcemia , hypoparathyroidism , Hypoxia , Idiopathic Generalized Epilepsy , Idiopathic Generalized Epilepsy 8 , intellectual disability , myocardial infarction , Myocardial Reperfusion Injury , nemaline myopathy 2 , nephrolithiasis , Neurodevelopmental Disorders , parathyroid adenoma , primary hyperparathyroidism , Primary Lymphedema with Myelodysplasia , prostate cancer , pulmonary hypertension , rickets , secondary hyperparathyroidism Flna adrenoleukodystrophy , Aneurysm , aortic aneurysm , Arterial Thrombosis , arterial tortuosity syndrome , autistic disorder , autosomal hemophilia A , autosomal recessive limb-girdle muscular dystrophy type 2J , Barth syndrome , Breast Neoplasms , centronuclear myopathy 2 , cerebral creatine deficiency syndrome 1 , cleft palate , colitis , congenital heart disease , congenital myopathy 5 , connective tissue disease , craniosynostosis , Developmental Disabilities , disorder of sexual development , Dwarfism , dyskeratosis congenita , Ehlers-Danlos syndrome , Ehlers-Danlos syndrome classic type 1 , Emery-Dreifuss muscular dystrophy , epilepsy , Experimental Liver Cirrhosis , factor VIII deficiency , Familial Sudden Death , Familial Thoracic Aortic Aneurysm 2 , favism , FG syndrome , FG Syndrome 2 , frontometaphyseal dysplasia , frontometaphyseal dysplasia 1 , Gastrointestinal Hemorrhage , genetic disease , hemorrhagic disease , hepatoblastoma , hereditary breast ovarian cancer syndrome , hydronephrosis , immunodeficiency 33 , intellectual disability , Juberg Hayward Syndrome , Laterality Defects, Autosomal Dominant , Marfan syndrome , Melnick-Needles syndrome , methylmalonic acidemia and homocysteinemia cblX type , microcephaly , mitral valve prolapse , Muscle Hypotonia , myopia , NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, ARTHROGRYPOSIS, AND STRUCTURAL BRAIN ANOMALIES , Neurodevelopmental Disorders , Nijmegen breakage syndrome , omphalocele , orofacial cleft , osteochondrodysplasia , otopalatodigital syndrome spectrum disorder , otopalatodigital syndrome type 1 , otopalatodigital syndrome type 2 , paraplegia , patent foramen ovale , periventricular nodular heterotopia , Periventricular Nodular Heterotopia 4 , Phyllodes Tumor , prune belly syndrome , scoliosis , severe congenital encephalopathy due to MECP2 mutation , Splenomegaly , syndromic X-linked intellectual disability Lubs type , terminal osseous dysplasia , thoracic aortic aneurysm , thrombocytopenia , tuberous sclerosis , ventricular septal defect , Wolff-Parkinson-White syndrome , X-linked cardiac valvular dysplasia , X-linked chronic idiopathic intestinal pseudo-obstruction Grk2 Aicardi-Goutieres Syndrome 3 , allergic contact dermatitis , asphyxiating thoracic dystrophy , bacterial pneumonia , Burns , Cardiomegaly , cardiomyopathy , cardiovascular system disease , Cocaine-Related Disorders , Congenital Abnormalities , congestive heart failure , Diabetic Nephropathies , Embryo Loss , Experimental Arthritis , Experimental Autoimmune Myocarditis , Experimental Liver Cirrhosis , Hyperalgesia , hyperglycemia , hypertension , immunodeficiency 90 , impotence , Insulin Resistance , intellectual disability , Left Ventricular Hypertrophy , limb ischemia , liver cirrhosis , Myocardial Reperfusion Injury , Neuralgia , opiate dependence , Parkinson's disease , pituitary adenoma , portal hypertension , Pruritus , rheumatoid arthritis , Right Ventricular Hypertrophy , Sepsis , toxic shock syndrome , Vascular System Injuries Grk3 bipolar disorder , Cardiomegaly , Cocaine-Related Disorders , congestive heart failure , Diabetic Nephropathies , hypertension , hypothyroidism , Parkinson's disease Grk4 Chemical and Drug Induced Liver Injury , cherubism , Diabetic Nephropathies , Ellis-Van Creveld syndrome , essential hypertension , fetal akinesia deformation sequence syndrome 1 Rgs12 cherubism , Ellis-Van Creveld syndrome , fetal akinesia deformation sequence syndrome 1 , schizophrenia Rgs2 acute myeloid leukemia , bladder disease , Breast Neoplasms , Experimental Liver Cirrhosis , female stress incontinence , gastrointestinal stromal tumor , glomerulosclerosis , Hyperparathyroidism 1 , hypertension , liver cirrhosis , opioid abuse , parathyroid carcinoma , secondary Parkinson disease , Stomach Neoplasms Rgs4 alcohol dependence , bladder disease , Drug-Induced Dyskinesia , endometriosis , epilepsy , Experimental Seizures , gastrointestinal stromal tumor , Hyperalgesia , hypertension , lesion of sciatic nerve , opioid abuse , parathyroid carcinoma , Parkinsonism , status epilepticus Rgs5 colorectal adenocarcinoma , essential hypertension , Experimental Liver Cirrhosis , gastrointestinal stromal tumor , hypertension , parathyroid carcinoma Rhoa Abnormalities, Drug-Induced , acute myocardial infarction , Aicardi-Goutieres Syndrome 1 , alopecia , Animal Disease Models , asthma , autosomal recessive limb-girdle muscular dystrophy type 2P , Brain Injuries , breast cancer , breast carcinoma , carcinoma , Cardiomegaly , carnitine-acylcarnitine translocase deficiency , Cocaine-Related Disorders , colorectal cancer , congenital diaphragmatic hernia , Craniofacial Abnormalities , Diabetic Nephropathies , ectodermal dysplasia , ECTODERMAL DYSPLASIA WITH FACIAL DYSMORPHISM AND ACRAL, OCULAR, AND BRAIN ANOMALIES , Experimental Autoimmune Encephalomyelitis , Experimental Autoimmune Neuritis , Experimental Diabetes Mellitus , Experimental Liver Cirrhosis , fetal alcohol syndrome , Fibrosis , genetic disease , Germ Cell and Embryonal Neoplasms , glycine encephalopathy , hypertension , Hypopigmentation , Immunoblastic Lymphadenopathy , Left Ventricular Hypertrophy , Leukoencephalopathies , Lymphatic Metastasis , membranous glomerulonephritis , multiple sclerosis , Myocardial Reperfusion Injury , Neoplasm Invasiveness , Neoplasm Metastasis , Neurocutaneous Syndromes , obesity , Optic Nerve Injuries , ovarian carcinoma , peripheral T-cell lymphoma , Pierson syndrome , primary biliary cholangitis , primary cutaneous T-cell non-Hodgkin lymphoma , proteinuria , pulmonary hypertension , Spinal Cord Injuries , Stomach Neoplasms , T-cell non-Hodgkin lymphoma , tooth disease , urinary bladder cancer , Urologic Neoplasms , withdrawal disorder
3-methylglutaconic aciduria type 7b Arrb1 Abnormalities, Drug-Induced Rhoa acute myeloid leukemia Rgs2 acute myocardial infarction Rhoa adrenoleukodystrophy Flna Aicardi-Goutieres Syndrome 1 Rhoa Aicardi-Goutieres Syndrome 3 Grk2 Albuminuria Casr alcohol dependence Arrb2 , Rgs4 alkaptonuria Casr allergic contact dermatitis Grk2 alopecia Rhoa amphetamine abuse Arrb2 Aneurysm Flna Animal Disease Models Rhoa aortic aneurysm Flna Arterial Thrombosis Flna arterial tortuosity syndrome Flna Arteriovenous Fistula Arrb1 , Arrb2 asphyxiating thoracic dystrophy Grk2 asthma Rhoa atherosclerosis Casr autistic disorder Flna autosomal dominant hypocalcemia Casr autosomal dominant hypocalcemia 1 Casr Autosomal Dominant Hypocalcemia, with Bartter Syndrome Casr autosomal hemophilia A Flna autosomal recessive limb-girdle muscular dystrophy type 2J Flna autosomal recessive limb-girdle muscular dystrophy type 2P Rhoa bacterial pneumonia Grk2 Barth syndrome Flna Bartter disease type 3 Casr bipolar disorder Grk3 bladder disease Rgs2 , Rgs4 brain infarction Arrb2 Brain Injuries Rhoa breast cancer Casr , Rhoa breast carcinoma Rhoa Breast Neoplasms Flna , Rgs2 Burns Grk2 calcium oxalate nephrolithiasis Casr carcinoma Rhoa Cardiomegaly Grk2 , Grk3 , Rhoa cardiomyopathy Casr , Grk2 cardiovascular system disease Grk2 carnitine-acylcarnitine translocase deficiency Rhoa centronuclear myopathy 2 Flna cerebral creatine deficiency syndrome 1 Flna Chemical and Drug Induced Liver Injury Grk4 cherubism Grk4 , Rgs12 cleft palate Flna Cocaine-Related Disorders Grk2 , Grk3 , Rhoa colitis Arrb1 , Flna colorectal adenocarcinoma Rgs5 colorectal cancer Rhoa Congenital Abnormalities Grk2 congenital diaphragmatic hernia Rhoa congenital heart disease Flna congenital myopathy 5 Flna congestive heart failure Arrb1 , Grk2 , Grk3 connective tissue disease Flna Craniofacial Abnormalities Rhoa craniosynostosis Flna Developmental Disabilities Casr , Flna Diabetic Cardiomyopathies Casr Diabetic Nephropathies Grk2 , Grk3 , Grk4 , Rhoa disorder of sexual development Flna drug psychosis Arrb2 Drug-Induced Dyskinesia Rgs4 Dwarfism Flna dyskeratosis congenita Flna ectodermal dysplasia Rhoa ECTODERMAL DYSPLASIA WITH FACIAL DYSMORPHISM AND ACRAL, OCULAR, AND BRAIN ANOMALIES Rhoa Ehlers-Danlos syndrome Flna Ehlers-Danlos syndrome classic type 1 Flna Ellis-Van Creveld syndrome Grk4 , Rgs12 Embryo Loss Grk2 Emery-Dreifuss muscular dystrophy Flna end stage renal disease Casr endometriosis Rgs4 epilepsy Flna , Rgs4 essential hypertension Grk4 , Rgs5 Experimental Arthritis Arrb1 , Arrb2 , Grk2 Experimental Autoimmune Encephalomyelitis Rhoa Experimental Autoimmune Myocarditis Grk2 Experimental Autoimmune Neuritis Rhoa Experimental Diabetes Mellitus Casr , Rhoa Experimental Liver Cirrhosis Arrb2 , Flna , Grk2 , Rgs2 , Rgs5 , Rhoa Experimental Liver Neoplasms Arrb2 Experimental Seizures Rgs4 factor VIII deficiency Flna familial hypocalciuric hypercalcemia Casr familial hypocalciuric hypercalcemia 1 Casr familial isolated hypoparathyroidism Casr Familial Sudden Death Flna Familial Thoracic Aortic Aneurysm 2 Flna favism Flna female stress incontinence Rgs2 fetal akinesia deformation sequence syndrome 1 Grk4 , Rgs12 fetal alcohol syndrome Rhoa FG syndrome Flna FG Syndrome 2 Flna Fibrosis Rhoa frontometaphyseal dysplasia Flna frontometaphyseal dysplasia 1 Flna Gastrointestinal Hemorrhage Flna gastrointestinal stromal tumor Rgs2 , Rgs4 , Rgs5 genetic disease Casr , Flna , Rhoa Germ Cell and Embryonal Neoplasms Rhoa Gitelman syndrome Casr glioblastoma Arrb2 glomerulosclerosis Rgs2 glycine encephalopathy Rhoa hemorrhagic disease Flna hepatoblastoma Flna hepatocellular carcinoma Arrb2 hereditary breast ovarian cancer syndrome Flna Hereditary Neoplastic Syndromes Casr heroin dependence Arrb2 hydronephrosis Flna Hyperalgesia Grk2 , Rgs4 hypercalcemia Casr Hypercalciuria Casr hyperglycemia Grk2 hyperparathyroidism Casr Hyperparathyroidism 1 Rgs2 Hyperparathyroidism, Neonatal Severe Primary Casr hypertension Arrb2 , Grk2 , Grk3 , Rgs2 , Rgs4 , Rgs5 , Rhoa hypertrophic cardiomyopathy Casr Hypocalcemia Casr hypoparathyroidism Casr Hypopigmentation Rhoa hypothyroidism Grk3 Hypoxia Casr Idiopathic Generalized Epilepsy Casr Idiopathic Generalized Epilepsy 8 Casr Immunoblastic Lymphadenopathy Rhoa immunodeficiency 33 Flna immunodeficiency 90 Grk2 impotence Grk2 Insulin Resistance Grk2 intellectual disability Arrb1 , Casr , Flna , Grk2 Juberg Hayward Syndrome Flna Laterality Defects, Autosomal Dominant Flna Left Ventricular Hypertrophy Grk2 , Rhoa lesion of sciatic nerve Rgs4 Leukoencephalopathies Rhoa limb ischemia Grk2 liver cirrhosis Arrb1 , Arrb2 , Grk2 , Rgs2 Lymphatic Metastasis Rhoa major depressive disorder Arrb1 Marfan syndrome Flna Melnick-Needles syndrome Flna membranous glomerulonephritis Rhoa metabolic dysfunction and alcohol associated liver disease Arrb2 methylmalonic acidemia and homocysteinemia cblX type Flna microcephaly Flna mitral valve prolapse Flna multiple sclerosis Rhoa Muscle Hypotonia Flna myocardial infarction Casr Myocardial Reperfusion Injury Arrb2 , Casr , Grk2 , Rhoa myopia Flna nemaline myopathy 2 Casr Neoplasm Invasiveness Rhoa Neoplasm Metastasis Rhoa nephrolithiasis Casr Neuralgia Grk2 Neurocutaneous Syndromes Rhoa NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, ARTHROGRYPOSIS, AND STRUCTURAL BRAIN ANOMALIES Flna Neurodevelopmental Disorders Casr , Flna nicotine dependence Arrb2 Nijmegen breakage syndrome Flna obesity Rhoa omphalocele Flna opiate dependence Arrb2 , Grk2 opioid abuse Rgs2 , Rgs4 Optic Nerve Injuries Rhoa orofacial cleft Flna osteochondrodysplasia Flna otopalatodigital syndrome spectrum disorder Flna otopalatodigital syndrome type 1 Flna otopalatodigital syndrome type 2 Flna ovarian carcinoma Rhoa pain agnosia Arrb2 paraplegia Flna parathyroid adenoma Casr parathyroid carcinoma Rgs2 , Rgs4 , Rgs5 Parkinson's disease Grk2 , Grk3 Parkinsonism Rgs4 patent foramen ovale Flna peripheral T-cell lymphoma Rhoa periventricular nodular heterotopia Flna Periventricular Nodular Heterotopia 4 Flna Phyllodes Tumor Flna Pierson syndrome Rhoa pituitary adenoma Grk2 portal hypertension Arrb2 , Grk2 primary biliary cholangitis Rhoa primary cutaneous T-cell non-Hodgkin lymphoma Rhoa primary hyperparathyroidism Casr Primary Lymphedema with Myelodysplasia Casr prostate cancer Casr proteinuria Rhoa prune belly syndrome Flna Pruritus Grk2 pulmonary hypertension Casr , Rhoa renal fibrosis Arrb2 rheumatoid arthritis Grk2 rickets Casr Right Ventricular Hypertrophy Grk2 schizophrenia Rgs12 scoliosis Flna secondary hyperparathyroidism Casr secondary Parkinson disease Rgs2 Sepsis Grk2 severe congenital encephalopathy due to MECP2 mutation Flna Spinal Cord Injuries Rhoa Splenomegaly Flna status epilepticus Rgs4 Stomach Neoplasms Rgs2 , Rhoa syndromic X-linked intellectual disability Lubs type Flna T-cell non-Hodgkin lymphoma Rhoa terminal osseous dysplasia Flna thoracic aortic aneurysm Flna thrombocytopenia Flna tooth disease Rhoa toxic shock syndrome Grk2 Transplant Rejection Arrb1 , Arrb2 tuberous sclerosis Flna type 2 diabetes mellitus Arrb2 urinary bladder cancer Rhoa Urologic Neoplasms Rhoa Vascular System Injuries Grk2 ventricular septal defect Flna withdrawal disorder Rhoa Wolff-Parkinson-White syndrome Flna X-linked cardiac valvular dysplasia Flna X-linked chronic idiopathic intestinal pseudo-obstruction Flna
Pathway Annotations Associated with Genes in the calcium signaling pathway via the calcium-sensing receptor
Arrb1 angiotensin II signaling pathway via AT1 receptor , calcium signaling pathway via the calcium-sensing receptor , chemokine mediated signaling pathway , corticotropin-releasing hormone signaling pathway , dopamine signaling pathway via D1 family of receptors , dopamine signaling pathway via D2 family of receptors , endocytosis pathway , epinephrine signaling pathway via adrenergic receptor beta , kinin signaling pathway , mitogen activated protein kinase signaling pathway , parathyroid hormone signaling pathway , visual phototransduction pathway Arrb2 angiotensin II signaling pathway via AT1 receptor , calcium signaling pathway via the calcium-sensing receptor , chemokine mediated signaling pathway , corticotropin-releasing hormone signaling pathway , dopamine signaling pathway via D1 family of receptors , dopamine signaling pathway via D2 family of receptors , eicosanoid signaling pathway , endocytosis pathway , epinephrine signaling pathway via adrenergic receptor beta , Hedgehog signaling pathway , kinin signaling pathway , mitogen activated protein kinase signaling pathway , nuclear factor kappa B signaling pathway , parathyroid hormone signaling pathway , transforming growth factor-beta Smad dependent signaling pathway , visual phototransduction pathway , Wnt signaling, non-canonical pathway Casr calcium signaling pathway via the calcium-sensing receptor , E-cadherin signaling pathway , G protein mediated signaling pathway via Galpha12/Galpha13 family , G protein mediated signaling pathway via Galphai family , G protein mediated signaling pathway via Galphaq family Flna calcium signaling pathway via the calcium-sensing receptor , integrin mediated signaling pathway , mitogen activated protein kinase signaling pathway , Rho/Rac/Cdc42 mediated signaling pathway , Wnt signaling, non-canonical pathway Grk2 acetylcholine signaling pathway via muscarinic acetylcholine receptor , angiotensin II signaling pathway via AT1 receptor , calcium signaling pathway via the calcium-sensing receptor , chemokine mediated signaling pathway , dopamine signaling pathway via D1 family of receptors , dopamine signaling pathway via D2 family of receptors , eicosanoid signaling pathway , endocytosis pathway , epinephrine signaling pathway via adrenergic receptor beta , G protein mediated signaling pathway , glutamate signaling pathway , Hedgehog signaling pathway , parathyroid hormone signaling pathway , somatostatin signaling pathway Grk3 angiotensin II signaling pathway via AT1 receptor , calcium signaling pathway via the calcium-sensing receptor , chemokine mediated signaling pathway , corticotropin-releasing hormone signaling pathway , dopamine signaling pathway via D1 family of receptors , dopamine signaling pathway via D2 family of receptors , eicosanoid signaling pathway , endocytosis pathway , G protein mediated signaling pathway , glutamate signaling pathway Grk4 calcium signaling pathway via the calcium-sensing receptor , chemokine mediated signaling pathway , endocytosis pathway , kinin signaling pathway Rgs12 calcium signaling pathway via the calcium-sensing receptor , G protein mediated signaling pathway via Galpha12/Galpha13 family Rgs2 acetylcholine signaling pathway via muscarinic acetylcholine receptor , angiotensin II signaling pathway via AT1 receptor , calcium signaling pathway via the calcium-sensing receptor , dopamine signaling pathway via D1 family of receptors , dopamine signaling pathway via D2 family of receptors , G protein mediated signaling pathway via Galphai family , G protein mediated signaling pathway via Galphaq family , G protein mediated signaling pathway via Galphas family Rgs4 acetylcholine signaling pathway via muscarinic acetylcholine receptor , calcium signaling pathway via the calcium-sensing receptor , dopamine signaling pathway via D1 family of receptors , dopamine signaling pathway via D2 family of receptors , G protein mediated signaling pathway via Galphai family , G protein mediated signaling pathway via Galphaq family , G protein mediated signaling pathway via Galphas family Rgs5 calcium signaling pathway via the calcium-sensing receptor , G protein mediated signaling pathway via Galphai family , G protein mediated signaling pathway via Galphaq family Rhoa calcium signaling pathway via the calcium-sensing receptor , chemokine mediated signaling pathway , colorectal cancer pathway , E-cadherin signaling pathway , eicosanoid signaling pathway , endocytosis pathway , endothelin signaling pathway , ephrin - ephrin receptor bidirectional signaling axis , interleukin-2 signaling pathway , mTOR signaling pathway , N-cadherin signaling pathway , neurotrophic factor signaling pathway , phosphatidylinositol 3-kinase class I signaling pathway , platelet-derived growth factor signaling pathway , Rho/Rac/Cdc42 mediated signaling pathway , sphingosine 1-phosphate signaling pathway , syndecan signaling pathway , T cell receptor signaling pathway , transforming growth factor-beta Smad dependent signaling pathway , transforming growth factor-beta superfamily mediated signaling pathway , tuberculosis pathway , vascular endothelial growth factor signaling pathway , Wnt signaling pathway , Wnt signaling, non-canonical pathway , Wnt signaling, the planar cell polarity pathway
acetylcholine signaling pathway via muscarinic acetylcholine receptor Grk2 , Rgs2 , Rgs4 angiotensin II signaling pathway via AT1 receptor Arrb1 , Arrb2 , Grk2 , Grk3 , Rgs2 calcium signaling pathway via the calcium-sensing receptor Arrb1 , Arrb2 , Casr , Flna , Grk2 , Grk3 , Grk4 , Rgs12 , Rgs2 , Rgs4 , Rgs5 , Rhoa chemokine mediated signaling pathway Arrb1 , Arrb2 , Grk2 , Grk3 , Grk4 , Rhoa colorectal cancer pathway Rhoa corticotropin-releasing hormone signaling pathway Arrb1 , Arrb2 , Grk3 dopamine signaling pathway via D1 family of receptors Arrb1 , Arrb2 , Grk2 , Grk3 , Rgs2 , Rgs4 dopamine signaling pathway via D2 family of receptors Arrb1 , Arrb2 , Grk2 , Grk3 , Rgs2 , Rgs4 E-cadherin signaling pathway Casr , Rhoa eicosanoid signaling pathway Arrb2 , Grk2 , Grk3 , Rhoa endocytosis pathway Arrb1 , Arrb2 , Grk2 , Grk3 , Grk4 , Rhoa endothelin signaling pathway Rhoa ephrin - ephrin receptor bidirectional signaling axis Rhoa epinephrine signaling pathway via adrenergic receptor beta Arrb1 , Arrb2 , Grk2 G protein mediated signaling pathway Grk2 , Grk3 G protein mediated signaling pathway via Galpha12/Galpha13 family Casr , Rgs12 G protein mediated signaling pathway via Galphai family Casr , Rgs2 , Rgs4 , Rgs5 G protein mediated signaling pathway via Galphaq family Casr , Rgs2 , Rgs4 , Rgs5 G protein mediated signaling pathway via Galphas family Rgs2 , Rgs4 glutamate signaling pathway Grk2 , Grk3 Hedgehog signaling pathway Arrb2 , Grk2 integrin mediated signaling pathway Flna interleukin-2 signaling pathway Rhoa kinin signaling pathway Arrb1 , Arrb2 , Grk4 mitogen activated protein kinase signaling pathway Arrb1 , Arrb2 , Flna mTOR signaling pathway Rhoa N-cadherin signaling pathway Rhoa neurotrophic factor signaling pathway Rhoa nuclear factor kappa B signaling pathway Arrb2 parathyroid hormone signaling pathway Arrb1 , Arrb2 , Grk2 phosphatidylinositol 3-kinase class I signaling pathway Rhoa platelet-derived growth factor signaling pathway Rhoa Rho/Rac/Cdc42 mediated signaling pathway Flna , Rhoa somatostatin signaling pathway Grk2 sphingosine 1-phosphate signaling pathway Rhoa syndecan signaling pathway Rhoa T cell receptor signaling pathway Rhoa transforming growth factor-beta Smad dependent signaling pathway Arrb2 , Rhoa transforming growth factor-beta superfamily mediated signaling pathway Rhoa tuberculosis pathway Rhoa vascular endothelial growth factor signaling pathway Rhoa visual phototransduction pathway Arrb1 , Arrb2 Wnt signaling pathway Rhoa Wnt signaling, non-canonical pathway Arrb2 , Flna , Rhoa Wnt signaling, the planar cell polarity pathway Rhoa
References Associated with the calcium signaling pathway via the calcium-sensing receptor:
Thomsen AR, etal., Cell Calcium. 2012 Feb;51(2):107-16. doi: 10.1016/j.ceca.2011.11.009. Epub 2011 Dec 20.
Pi M, etal., Mol Endocrinol. 2005 Apr;19(4):1078-87. Epub 2005 Jan 6.
Pi M, etal., Endocrinology. 2002 Oct;143(10):3830-8.
Koh J, etal., Mol Endocrinol. 2011 May;25(5):867-76. doi: 10.1210/me.2010-0277. Epub 2011 Mar 10.
Brown EM and MacLeod RJ, Physiol Rev. 2001 Jan;81(1):239-297.
Magno AL, etal., Endocr Rev. 2011 Feb;32(1):3-30. doi: 10.1210/er.2009-0043. Epub 2010 Aug 20.
Ward DT and Riccardi D, Br J Pharmacol. 2012 Jan;165(1):35-48. doi: 10.1111/j.1476-5381.2011.01511.x.
Huang C and Miller RT, Curr Opin Nephrol Hypertens. 2010 Jan;19(1):106-12. doi: 10.1097/MNH.0b013e328332e7b2.
Khan MA and Conigrave AD, Br J Pharmacol. 2010 Mar;159(5):1039-50. doi: 10.1111/j.1476-5381.2009.00603.x. Epub 2010 Feb 5.
Huang C and Miller RT, J Cell Mol Med. 2007 Sep-Oct;11(5):923-34.
Saidak Z, etal., Mol Pharmacol. 2009 Dec;76(6):1131-44. doi: 10.1124/mol.109.058784. Epub 2009 Sep 24.
Nemeth EF J Mol Endocrinol. 2002 Aug;29(1):15-21.
Riccardi D, etal., Pflugers Arch. 2009 Oct;458(6):1007-22. doi: 10.1007/s00424-009-0681-z. Epub 2009 May 30.
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