KEGG   PATHWAY: ko04961
Entry
ko04961                     Pathway                                
Name
Endocrine and other factor-regulated calcium reabsorption
Description
Calcium (Ca2+) is essential for numerous physiological functions including intracellular signalling processes, neuronal excitability, muscle contraction and bone formation. Therefore, its homeostasis is finely maintained through the coordination of intestinal absorption, renal reabsorption, and bone resorption. In kidney, the late part of the distal convoluted tubule (DCT) and the connecting tubule (CNT) are the site of active Ca2+ transport and precisely regulate Ca2+ reabsorption. Following Ca2+ entry through TRPV5, Ca2+ bound to calbindin-D28K diffuses to the basolateral side, where it is extruded into the blood compartment through NCX1 and to a lesser extent PMCA1b. In the urinary compartment, both klotho and tissue kallikrein (TK) increase the apical abundance of TRPV5. In the blood compartment, PTH, 1,25(OH)2D3 and estrogen increase the transcription and protein expression of the luminal Ca2+ channels, calbindins, and the extrusion systems.
Class
Organismal Systems; Excretory system
Pathway map
ko04961  Endocrine and other factor-regulated calcium reabsorption
ko04961

Orthology
K01325  KLK1_2; tissue kallikrein [EC:3.4.21.35]
K01528  DNM1_3; dynamin 1/3 [EC:3.6.5.5]
K01538  FXYD2, ATP1G1; sodium/potassium-transporting ATPase subunit gamma (FXYD domain-containing ion transport regulator 2)
K01539  ATP1A; sodium/potassium-transporting ATPase subunit alpha [EC:7.2.2.13]
K01540  ATP1B, CD298; sodium/potassium-transporting ATPase subunit beta
K02677  PRKCA; classical protein kinase C alpha type [EC:2.7.11.13]
K03916  BDKRB2; bradykinin receptor B2
K04345  PKA; protein kinase A [EC:2.7.11.11]
K04585  PTH1R, PTHR1; parathyroid hormone receptor 1
K04632  GNAS; guanine nucleotide-binding protein G(s) subunit alpha
K04634  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha
K04644  CLTA, LCA; clathrin light chain A
K04645  CLTB, LCB; clathrin light chain B
K04646  CLTC; clathrin heavy chain
K04974  TRPV5; transient receptor potential cation channel subfamily V member 5
K05261  PTH; parathyroid hormone
K05849  SLC8A, NCX; solute carrier family 8 (sodium/calcium exchanger)
K05850  ATP2B; P-type Ca2+ transporter type 2B [EC:7.2.2.10]
K05858  PLCB; phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K07904  RAB11A; Ras-related protein Rab-11A
K08046  ADCY6; adenylate cyclase 6 [EC:4.6.1.1]
K08049  ADCY9; adenylate cyclase 9 [EC:4.6.1.1]
K08539  VDR, NR1I1; vitamin D3 receptor
K08550  ESR1, NR3A1; estrogen receptor alpha
K11824  AP2A; AP-2 complex subunit alpha
K11825  AP2B1; AP-2 complex subunit beta-1
K11826  AP2M1; AP-2 complex subunit mu-1
K11827  AP2S1; AP-2 complex subunit sigma-1
K14756  KL; klotho [EC:3.2.1.31]
K14757  CALB1, CALB; calbindin
K19662  PRKCB; classical protein kinase C beta type [EC:2.7.11.13]
K19663  PRKCG; classical protein kinase C gamma type [EC:2.7.11.13]
K23484  DNM2; dynamin 2
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C00238  Potassium cation
C00575  3',5'-Cyclic AMP
C00951  Estradiol-17beta
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C01673  Calcitriol
Reference
  Authors
Boros S, Bindels RJ, Hoenderop JG
  Title
Active Ca(2+) reabsorption in the connecting tubule.
  Journal
Pflugers Arch 458:99-109 (2009)
DOI:10.1007/s00424-008-0602-6
Reference
  Authors
Lambers TT, Bindels RJ, Hoenderop JG
  Title
Coordinated control of renal Ca2+ handling.
  Journal
Kidney Int 69:650-4 (2006)
DOI:10.1038/sj.ki.5000169
Reference
  Authors
de Groot T, Bindels RJ, Hoenderop JG
  Title
TRPV5: an ingeniously controlled calcium channel.
  Journal
Kidney Int 74:1241-6 (2008)
DOI:10.1038/ki.2008.320
Reference
  Authors
Markadieu N, Bindels RJ, Hoenderop JG
  Title
The renal connecting tubule: Resolved and unresolved issues in Ca(2+) transport.
  Journal
Int J Biochem Cell Biol 43:1-4 (2011)
DOI:10.1016/j.biocel.2010.10.006
Reference
  Authors
Hoenderop JG, Nilius B, Bindels RJ
  Title
Calcium absorption across epithelia.
  Journal
Physiol Rev 85:373-422 (2005)
DOI:10.1152/physrev.00003.2004
Reference
  Authors
van Abel M, Hoenderop JG, Bindels RJ
  Title
The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease.
  Journal
Naunyn Schmiedebergs Arch Pharmacol 371:295-306 (2005)
DOI:10.1007/s00210-005-1021-2
Reference
  Authors
Nijenhuis T, Hoenderop JG, Bindels RJ
  Title
TRPV5 and TRPV6 in Ca(2+) (re)absorption: regulating Ca(2+) entry at the gate.
  Journal
Pflugers Arch 451:181-92 (2005)
DOI:10.1007/s00424-005-1430-6
Reference
  Authors
Hoenderop JG, Nilius B, Bindels RJ
  Title
Epithelial calcium channels: from identification to function and regulation.
  Journal
Pflugers Arch 446:304-8 (2003)
DOI:10.1007/s00424-003-1045-8
Reference
  Authors
Gkika D, Topala CN, Chang Q, Picard N, Thebault S, Houillier P, Hoenderop JG, Bindels RJ
  Title
Tissue kallikrein stimulates Ca(2+) reabsorption via PKC-dependent plasma membrane accumulation of TRPV5.
  Journal
EMBO J 25:4707-16 (2006)
DOI:10.1038/sj.emboj.7601357
Reference
  Authors
Schoeber JP, Hoenderop JG, Bindels RJ
  Title
Concerted action of associated proteins in the regulation of TRPV5 and TRPV6.
  Journal
Biochem Soc Trans 35:115-9 (2007)
DOI:10.1042/BST0350115
Reference
  Authors
Renkema KY, Alexander RT, Bindels RJ, Hoenderop JG
  Title
Calcium and phosphate homeostasis: concerted interplay of new regulators.
  Journal
Ann Med 40:82-91 (2008)
DOI:10.1080/07853890701689645
Reference
  Authors
de Groot T, Lee K, Langeslag M, Xi Q, Jalink K, Bindels RJ, Hoenderop JG
  Title
Parathyroid hormone activates TRPV5 via PKA-dependent phosphorylation.
  Journal
J Am Soc Nephrol 20:1693-704 (2009)
DOI:10.1681/ASN.2008080873
Related
pathway
ko04144  Endocytosis
ko04530  Tight junction

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