Pkd1

Summary

Gene Symbol: Pkd1
Description: polycystin 1, transient receptor poteintial channel interacting
Alias: PC1, mFLJ00285, polycystin-1, autosomal dominant polycystic kidney disease 1 protein homolog, polycystic kidney disease 1 homolog, polycystic kidney disease 1 homolog; polycystin-1, polycystin 1
Species: mouse
Products:     Pkd1

Top Publications

  1. Wildman S, Hooper K, Turner C, Sham J, Lakatta E, King B, et al. The isolated polycystin-1 cytoplasmic COOH terminus prolongs ATP-stimulated Cl- conductance through increased Ca2+ entry. Am J Physiol Renal Physiol. 2003;285:F1168-78 pubmed
    The precise steps leading from mutation of the polycystic kidney disease (PKD1) gene to the autosomal dominant polycystic kidney disease (ADPKD) phenotype remain to be established...
  2. Yu S, Hackmann K, Gao J, Gao J, He X, Piontek K, et al. Essential role of cleavage of Polycystin-1 at G protein-coupled receptor proteolytic site for kidney tubular structure. Proc Natl Acad Sci U S A. 2007;104:18688-93 pubmed
    ..To investigate the role of cleavage in vivo, we generated by gene targeting a Pkd1 knockin mouse (Pkd1(V/V)) that expresses noncleavable PC1...
  3. Shillingford J, Piontek K, Germino G, Weimbs T. Rapamycin ameliorates PKD resulting from conditional inactivation of Pkd1. J Am Soc Nephrol. 2010;21:489-97 pubmed publisher
    ..are highly effective in several rodent models of PKD, but these models result from mutations in genes other than Pkd1 and Pkd2, which are the primary genes responsible for human autosomal dominant PKD...
  4. Guillaume R, D AGATI V, Daoust M, Trudel M. Murine Pkd1 is a developmentally regulated gene from morula to adulthood: role in tissue condensation and patterning. Dev Dyn. 1999;214:337-48 pubmed
    b>PKD1 is the most common genetically mutated gene involved in autosomal dominant polycystic kidney disease (ADPKD)...
  5. Boulter C, Mulroy S, Webb S, Fleming S, Brindle K, Sandford R. Cardiovascular, skeletal, and renal defects in mice with a targeted disruption of the Pkd1 gene. Proc Natl Acad Sci U S A. 2001;98:12174-9 pubmed
    ..It is caused by mutations in PKD1 or PKD2, encoding polycystin-1 and -2, which together form a cell surface nonselective cation ion channel...
  6. Kolpakova Hart E, McBratney Owen B, Hou B, Fukai N, Nicolae C, Zhou J, et al. Growth of cranial synchondroses and sutures requires polycystin-1. Dev Biol. 2008;321:407-19 pubmed publisher
    ..restricted growth defects at the skull base and in craniofacial sutures of mice deficient for polycystin-1 (Pkd1)...
  7. Piontek K, Menezes L, Garcia Gonzalez M, Huso D, Germino G. A critical developmental switch defines the kinetics of kidney cyst formation after loss of Pkd1. Nat Med. 2007;13:1490-5 pubmed
    ..Mutations in PKD1 (the gene encoding polycystin-1) are the principal cause of this disease...
  8. Xiao Z, Zhang S, Magenheimer B, Luo J, Quarles L. Polycystin-1 regulates skeletogenesis through stimulation of the osteoblast-specific transcription factor RUNX2-II. J Biol Chem. 2008;283:12624-34 pubmed publisher
    ..To establish the role of Runx2-II in mediating PC1 effects on bone, we crossed heterozygous Pkd1(m1Bei) and Runx2-II mice to create double heterozygous mice (Pkd1(+/m1Bei)/Runx2-II(+/-)) deficient in both PC1 and ..
  9. Nauli S, Kawanabe Y, Kaminski J, Pearce W, Ingber D, Zhou J. Endothelial cilia are fluid shear sensors that regulate calcium signaling and nitric oxide production through polycystin-1. Circulation. 2008;117:1161-71 pubmed publisher
    ..Cells with the Pkd1(null/null) or Tg737(orpk/orpk) mutation encoded for polycystin-1 or polaris, respectively, are unable to transmit ..

More Information

Publications71

  1. Xiao Z, Dallas M, Qiu N, NICOLELLA D, Cao L, Johnson M, et al. Conditional deletion of Pkd1 in osteocytes disrupts skeletal mechanosensing in mice. FASEB J. 2011;25:2418-32 pubmed publisher
    We investigated whether polycystin-1 is a bone mechanosensor. We conditionally deleted Pkd1 in mature osteoblasts/osteocytes by crossing Dmp1-Cre with Pkd1(flox/m1Bei) mice, in which the m1Bei allele is nonfunctional...
  2. Sharif Naeini R, Folgering J, Bichet D, Duprat F, Lauritzen I, Arhatte M, et al. Polycystin-1 and -2 dosage regulates pressure sensing. Cell. 2009;139:587-96 pubmed publisher
    ..polycystic kidney disease, the most frequent monogenic cause of kidney failure, is induced by mutations in the PKD1 or PKD2 genes, encoding polycystins TRPP1 and TRPP2, respectively...
  3. Muto S, Aiba A, Saito Y, Nakao K, Nakamura K, Tomita K, et al. Pioglitazone improves the phenotype and molecular defects of a targeted Pkd1 mutant. Hum Mol Genet. 2002;11:1731-42 pubmed
    Mutations of either PKD1 or PKD2 are associated with autosomal dominant polycystic kidney disease (ADPKD)...
  4. Hopp K, Ward C, Hommerding C, Nasr S, Tuan H, Gainullin V, et al. Functional polycystin-1 dosage governs autosomal dominant polycystic kidney disease severity. J Clin Invest. 2012;122:4257-73 pubmed publisher
    Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations to PKD1 or PKD2, triggering progressive cystogenesis and typically leading to end-stage renal disease in midlife...
  5. Wodarczyk C, Rowe I, Chiaravalli M, Pema M, Qian F, Boletta A. A novel mouse model reveals that polycystin-1 deficiency in ependyma and choroid plexus results in dysfunctional cilia and hydrocephalus. PLoS ONE. 2009;4:e7137 pubmed publisher
    Polycystin-1 (PC-1), the product of the PKD1 gene, mutated in the majority of cases of Autosomal Dominant Polycystic Kidney Disease (ADPKD), is a very large (approximately 520 kDa) plasma membrane receptor localized in several subcellular ..
  6. Tran U, Zakin L, Schweickert A, Agrawal R, D ger R, Blum M, et al. The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity. Development. 2010;137:1107-16 pubmed publisher
    ..Based on these data, we propose that the kidney phenotype in Bicc1(-/-) mutant mice is caused by dysregulation of a microRNA-based translational control mechanism...
  7. Fielitz J, Kim M, Shelton J, Qi X, Hill J, Richardson J, et al. Requirement of protein kinase D1 for pathological cardiac remodeling. Proc Natl Acad Sci U S A. 2008;105:3059-63 pubmed publisher
    ..To test whether PKD1 is required for pathological cardiac remodeling in vivo, we generated mice with a conditional PKD1-null allele...
  8. Woodward O, Li Y, Yu S, Greenwell P, Wodarczyk C, Boletta A, et al. Identification of a polycystin-1 cleavage product, P100, that regulates store operated Ca entry through interactions with STIM1. PLoS ONE. 2010;5:e12305 pubmed publisher
    ..Mutations in either the PKD1 or PKD2/TRPP2 genes and their respective protein products, polycystin-1 (PC1) and polycystin-2 (PC2) result in ..
  9. Thivierge C, Kurbegovic A, Couillard M, Guillaume R, Côté O, Trudel M. Overexpression of PKD1 causes polycystic kidney disease. Mol Cell Biol. 2006;26:1538-48 pubmed
    ..While there is evidence that Pkd1 gene haploinsufficiency and loss of heterozygosity can cause cyst formation in mice, paradoxically high levels of ..
  10. Jiang S, Chiou Y, Wang E, Lin H, Lin Y, Chi Y, et al. Defining a link with autosomal-dominant polycystic kidney disease in mice with congenitally low expression of Pkd1. Am J Pathol. 2006;168:205-20 pubmed
    ..Mouse models for autosomal-dominant polycystic kidney disease (ADPKD), derived from homozygous targeted disruption of Pkd1 gene, generally die in utero or perinatally because of systemic defects...
  11. Allen E, Piontek K, Garrett Mayer E, Garcia Gonzalez M, Gorelick K, Germino G. Loss of polycystin-1 or polycystin-2 results in dysregulated apolipoprotein expression in murine tissues via alterations in nuclear hormone receptors. Hum Mol Genet. 2006;15:11-21 pubmed
    Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations of PKD1 and PKD2...
  12. Garcia Gonzalez M, Menezes L, Piontek K, Kaimori J, Huso D, Watnick T, et al. Genetic interaction studies link autosomal dominant and recessive polycystic kidney disease in a common pathway. Hum Mol Genet. 2007;16:1940-50 pubmed
    ..We then tested for genetic interaction between Pkhd1 and Pkd1, the mouse orthologue of the gene most commonly linked to human autosomal dominant PKD...
  13. Chauvet V, Tian X, Husson H, Grimm D, Wang T, Hiesberger T, et al. Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus. J Clin Invest. 2004;114:1433-43 pubmed
    ..Polycystin-2, the product of the second gene mutated in ADPKD, modulates the signaling properties of the polycystin-1 CTT. These data reveal a novel pathway by which polycystin-1 transmits messages directly to the nucleus. ..
  14. Wodarczyk C, Distefano G, Rowe I, Gaetani M, Bricoli B, Muorah M, et al. Nephrocystin-1 forms a complex with polycystin-1 via a polyproline motif/SH3 domain interaction and regulates the apoptotic response in mammals. PLoS ONE. 2010;5:e12719 pubmed publisher
    Mutations in PKD1, the gene encoding for the receptor Polycystin-1 (PC-1), cause autosomal dominant polycystic kidney disease (ADPKD)...
  15. Fan L, Li X, Magenheimer B, Calvet J, Li X. Inhibition of histone deacetylases targets the transcription regulator Id2 to attenuate cystic epithelial cell proliferation. Kidney Int. 2012;81:76-85 pubmed publisher
    ..The loss of Pkd1 caused an upregulation of the inhibitor of differentiation 2 (Id2), a transcription regulator, triggering an Id2-..
  16. Joly D, Ishibe S, Nickel C, Yu Z, Somlo S, Cantley L. The polycystin 1-C-terminal fragment stimulates ERK-dependent spreading of renal epithelial cells. J Biol Chem. 2006;281:26329-39 pubmed
    b>Polycystin 1, the product of the PKD1 gene, is mutated in autosomal dominant polycystic kidney disease, a disease characterized by renal cyst formation and progressive renal failure...
  17. Xia S, Li X, Johnson T, Seidel C, Wallace D, Li R. Polycystin-dependent fluid flow sensing targets histone deacetylase 5 to prevent the development of renal cysts. Development. 2010;137:1075-84 pubmed publisher
    b>Polycystin 1 and polycystin 2 are large transmembrane proteins, which, when mutated, cause autosomal dominant polycystic kidney disease (ADPKD), a highly prevalent human genetic disease...
  18. Seeger Nukpezah T, Proia D, Egleston B, Nikonova A, Kent T, Cai K, et al. Inhibiting the HSP90 chaperone slows cyst growth in a mouse model of autosomal dominant polycystic kidney disease. Proc Natl Acad Sci U S A. 2013;110:12786-91 pubmed publisher
    ..of 1:500 in the population, arising from inherited mutations in the genes for polycystic kidney disease 1 (PKD1) or polycystic kidney disease 2 (PKD2)...
  19. Boca M, D Amato L, Distefano G, Polishchuk R, Germino G, Boletta A. Polycystin-1 induces cell migration by regulating phosphatidylinositol 3-kinase-dependent cytoskeletal rearrangements and GSK3beta-dependent cell cell mechanical adhesion. Mol Biol Cell. 2007;18:4050-61 pubmed
    Polycystin-1 (PC-1) is a large plasma-membrane receptor encoded by the PKD1 gene mutated in autosomal dominant polycystic kidney disease (ADPKD)...
  20. Lu W, Peissel B, Babakhanlou H, Pavlova A, Geng L, Fan X, et al. Perinatal lethality with kidney and pancreas defects in mice with a targetted Pkd1 mutation. Nat Genet. 1997;17:179-81 pubmed
    b>PKD1 is the most common site for mutations in human autosomal dominant polycystic kidney disease (ADPKD). ADPKD is characterized by progressive replacement of kidney tissue by epithelial cysts and eventual renal failure...
  21. Qiu N, Xiao Z, Cao L, David V, Quarles L. Conditional mesenchymal disruption of pkd1 results in osteopenia and polycystic kidney disease. PLoS ONE. 2012;7:e46038 pubmed publisher
    Conditional deletion of Pkd1 in osteoblasts using either Osteocalcin(Oc)-Cre or Dmp1-Cre results in defective osteoblast-mediated postnatal bone formation and osteopenia...
  22. Lantinga van Leeuwen I, Dauwerse J, Baelde H, Leonhard W, van de Wal A, Ward C, et al. Lowering of Pkd1 expression is sufficient to cause polycystic kidney disease. Hum Mol Genet. 2004;13:3069-77 pubmed
    ..It is a systemic disorder that is caused by mutations in PKD1 or PKD2...
  23. Fedeles S, Tian X, Gallagher A, Mitobe M, Nishio S, Lee S, et al. A genetic interaction network of five genes for human polycystic kidney and liver diseases defines polycystin-1 as the central determinant of cyst formation. Nat Genet. 2011;43:639-47 pubmed publisher
  24. Spirli C, Okolicsanyi S, Fiorotto R, Fabris L, Cadamuro M, Lecchi S, et al. ERK1/2-dependent vascular endothelial growth factor signaling sustains cyst growth in polycystin-2 defective mice. Gastroenterology. 2010;138:360-371.e7 pubmed publisher
    ..can complicate adult dominant polycystic kidney disease, a genetic disease caused by defects in polycystin-1 (Pkd1) or polycystin-2 (Pkd2)...
  25. Nauli S, Rossetti S, Kolb R, Alenghat F, Consugar M, Harris P, et al. Loss of polycystin-1 in human cyst-lining epithelia leads to ciliary dysfunction. J Am Soc Nephrol. 2006;17:1015-25 pubmed
    ..It was reported previously that Pkd1(null/null) mouse kidney epithelial cells are unresponsive to flow stimulation...
  26. Nauli S, Alenghat F, Luo Y, Williams E, Vassilev P, Li X, et al. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet. 2003;33:129-37 pubmed
    ..Here, we show that polycystin-1 (PC1) and polycystin-2 (PC2), proteins respectively encoded by Pkd1 and Pkd2, mouse orthologs of genes mutated in human autosomal dominant PKD, co-distribute in the primary cilia of ..
  27. Yoder B, Hou X, Guay Woodford L. The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia. J Am Soc Nephrol. 2002;13:2508-16 pubmed
    ..To begin to address this issue, the expression of the protein products encoded by the PKD1, PKD2, Tg737, and cpk genes were examined in mouse cortical collecting duct (mCCD) cells using an ..
  28. Bhunia A, Piontek K, Boletta A, Liu L, Qian F, Xu P, et al. PKD1 induces p21(waf1) and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2. Cell. 2002;109:157-68 pubmed
    ..kidney disease is characterized by cyst formation in the kidney and other organs and results from mutations of PKD1 or PKD2. Previous studies suggest that their gene products have an important role in growth regulation...
  29. Kolpakova Hart E, Nicolae C, Zhou J, Olsen B. Col2-Cre recombinase is co-expressed with endogenous type II collagen in embryonic renal epithelium and drives development of polycystic kidney disease following inactivation of ciliary genes. Matrix Biol. 2008;27:505-12 pubmed publisher
    ..We demonstrate that conditional ablation of the Kif3a or Pkd1 genes encoding primary cilium/intraflagellar transport-associated proteins using type II collagen-specific Cre ..
  30. Battini L, Macip S, Fedorova E, Dikman S, Somlo S, Montagna C, et al. Loss of polycystin-1 causes centrosome amplification and genomic instability. Hum Mol Genet. 2008;17:2819-33 pubmed publisher
    ..disease (ADPKD) is the most common monogenetic disease predominantly caused by alteration or dysregulation of the PKD1 gene, which encodes polycystin-1 (PC1)...
  31. Su X, Driscoll K, Yao G, Raed A, Wu M, Beales P, et al. Bardet-Biedl syndrome proteins 1 and 3 regulate the ciliary trafficking of polycystic kidney disease 1 protein. Hum Mol Genet. 2014;23:5441-51 pubmed publisher
    ..receptor 3 or the leptin receptor that interacts with all subunits of the BBSome, the ADPKD protein polycystin-1 (PC1) interacts with BBS1, BBS4, BBS5 and BBS8, four of the seven components of the BBSome...
  32. Wu G, Tian X, Nishimura S, Markowitz G, D AGATI V, Park J, et al. Trans-heterozygous Pkd1 and Pkd2 mutations modify expression of polycystic kidney disease. Hum Mol Genet. 2002;11:1845-54 pubmed
    Autosomal dominant polycystic kidney disease (ADPKD) occurs by germline mutation in PKD1 or PKD2...
  33. Cebotaru V, Cebotaru L, Kim H, Chiaravalli M, Boletta A, Qian F, et al. Polycystin-1 negatively regulates Polycystin-2 expression via the aggresome/autophagosome pathway. J Biol Chem. 2014;289:6404-14 pubmed publisher
    Mutations of the PKD1 and PKD2 genes, encoding polycystin-1 (PC1) and polycystin-2 (PC2), respectively, lead to autosomal dominant polycystic kidney disease...
  34. Castelli M, Boca M, Chiaravalli M, Ramalingam H, Rowe I, Distefano G, et al. Polycystin-1 binds Par3/aPKC and controls convergent extension during renal tubular morphogenesis. Nat Commun. 2013;4:2658 pubmed publisher
    ..Most polycystic kidney disease cases result from loss-of-function mutations in the PKD1 gene, encoding Polycystin-1, a large receptor of unknown function...
  35. Luyten A, Su X, Gondela S, Chen Y, Rompani S, Takakura A, et al. Aberrant regulation of planar cell polarity in polycystic kidney disease. J Am Soc Nephrol. 2010;21:1521-32 pubmed publisher
    Mutations in PKD1, which encodes polycystin-1 (PC1), contribute to >85% of cases of autosomal dominant polycystic kidney disease (ADPKD)...
  36. Xiao Z, Zhang S, Cao L, Qiu N, David V, Quarles L. Conditional disruption of Pkd1 in osteoblasts results in osteopenia due to direct impairment of bone formation. J Biol Chem. 2010;285:1177-87 pubmed publisher
    b>PKD1 (polycystin-1), the disease-causing gene for ADPKD, is widely expressed in various cell types, including osteoblasts, where its function is unknown...
  37. Bertuccio C, Chapin H, Cai Y, Mistry K, Chauvet V, Somlo S, et al. Polycystin-1 C-terminal cleavage is modulated by polycystin-2 expression. J Biol Chem. 2009;284:21011-26 pubmed publisher
    ..This effect is independent of Ca2+ but is regulated by sequences contained within the PC-2 C-terminal tail, suggesting a mechanism through which PC-1 and PC-2 may modulate a novel signaling pathway. ..
  38. Kurbegovic A, Kim H, Xu H, Yu S, Cruanès J, Maser R, et al. Novel functional complexity of polycystin-1 by GPS cleavage in vivo: role in polycystic kidney disease. Mol Cell Biol. 2014;34:3341-53 pubmed publisher
    ..By functional genetic complementation with five Pkd1 mouse models, we discovered that CTF plays a crucial role in Pc1(deN) trafficking...
  39. Magenheimer B, St John P, Isom K, Abrahamson D, De Lisle R, Wallace D, et al. Early embryonic renal tubules of wild-type and polycystic kidney disease kidneys respond to cAMP stimulation with cystic fibrosis transmembrane conductance regulator/Na(+),K(+),2Cl(-) Co-transporter-dependent cystic dilation. J Am Soc Nephrol. 2006;17:3424-37 pubmed
    ..For determination of whether cystic dilation occurs to a greater extent in PKD kidneys in response to cAMP, Pkd1(m1Bei) -/- embryonic kidneys were treated with 8-Br-cAMP and were found to form rapidly CFTR- and Na(+),K(+),2Cl(-) ..
  40. Van Bodegom D, Saifudeen Z, Dipp S, Puri S, Magenheimer B, Calvet J, et al. The polycystic kidney disease-1 gene is a target for p53-mediated transcriptional repression. J Biol Chem. 2006;281:31234-44 pubmed
    This study provides evidence that the tumor suppressor protein, p53, is a transcriptional repressor of PKD1. Kidneys of p53-null mice expressed higher Pkd1 mRNA levels than wild-type littermates; gamma-irradiation suppressed PKD1 gene ..
  41. Lantinga van Leeuwen I, Leonhard W, van der Wal A, Breuning M, De Heer E, Peters D. Kidney-specific inactivation of the Pkd1 gene induces rapid cyst formation in developing kidneys and a slow onset of disease in adult mice. Hum Mol Genet. 2007;16:3188-96 pubmed
    Autosomal dominant polycystic kidney disease, caused by mutations in the PKD1 gene, is characterized by progressive deterioration of kidney function due to the formation of thousands of cysts leading to kidney failure in mid-life or later...
  42. Lu W, Shen X, Pavlova A, Lakkis M, Ward C, Pritchard L, et al. Comparison of Pkd1-targeted mutants reveals that loss of polycystin-1 causes cystogenesis and bone defects. Hum Mol Genet. 2001;10:2385-96 pubmed
    ..Here, we report the generation of a targeted mouse mutant with a null mutation in Pkd1 and its phenotypic characterization in comparison with the del34 mutants that carry a 'truncation mutation' in Pkd1...
  43. Hou B, Kolpakova Hart E, Fukai N, Wu K, Olsen B. The polycystic kidney disease 1 (Pkd1) gene is required for the responses of osteochondroprogenitor cells to midpalatal suture expansion in mice. Bone. 2009;44:1121-33 pubmed publisher
    ..bone labeling revealed that new bone formation in response to expansion was significantly reduced in Wnt1Cre;Pkd1 mice, as the suture area containing new bone was 14.0+/-3.4% in mutant mice versus 65.0+/-3...
  44. Geng L, Segal Y, Pavlova A, Barros E, Löhning C, Lu W, et al. Distribution and developmentally regulated expression of murine polycystin. Am J Physiol. 1997;272:F451-9 pubmed
    b>PKD1, the gene that is mutated in approximately 85% of autosomal dominant polycystic kidney disease (ADPKD) cases in humans, has recently been identified (Eur. PKD Consortium. Cell 77: 881-894, 1994; also, erratum in Cell 78: 1994)...
  45. Lu W, Fan X, Basora N, Babakhanlou H, Law T, Rifai N, et al. Late onset of renal and hepatic cysts in Pkd1-targeted heterozygotes. Nat Genet. 1999;21:160-1 pubmed
  46. Shibazaki S, Yu Z, Nishio S, Tian X, Thomson R, Mitobe M, et al. Cyst formation and activation of the extracellular regulated kinase pathway after kidney specific inactivation of Pkd1. Hum Mol Genet. 2008;17:1505-16 pubmed publisher
    ..Mice with kidney selective inactivation of Pkd1 during embryogenesis develop profound renal cystic disease and die from renal failure within 3 weeks of birth...
  47. Nishio S, Tian X, Gallagher A, Yu Z, Patel V, Igarashi P, et al. Loss of oriented cell division does not initiate cyst formation. J Am Soc Nephrol. 2010;21:295-302 pubmed publisher
    ..PKD, caused by mutations in PKHD1, is a developmental defect, whereas dominant PKD, caused by mutations in PKD1 or PKD2, occurs by a cellular recessive mechanism in mature kidneys...
  48. Kurbegovic A, Côté O, Couillard M, Ward C, Harris P, Trudel M. Pkd1 transgenic mice: adult model of polycystic kidney disease with extrarenal and renal phenotypes. Hum Mol Genet. 2010;19:1174-89 pubmed publisher
    While high levels of Pkd1 expression are detected in tissues of patients with autosomal dominant polycystic kidney disease (ADPKD), it is unclear whether enhanced expression could be a pathogenetic mechanism for this systemic disorder...
  49. Xiao Z, Zhang S, Mahlios J, Zhou G, Magenheimer B, Guo D, et al. Cilia-like structures and polycystin-1 in osteoblasts/osteocytes and associated abnormalities in skeletogenesis and Runx2 expression. J Biol Chem. 2006;281:30884-95 pubmed
    ..Pkd1m1Bei mice have inactivating missense mutations of Pkd1 gene that encode PC1...
  50. Piontek K, Huso D, Grinberg A, Liu L, Bedja D, Zhao H, et al. A functional floxed allele of Pkd1 that can be conditionally inactivated in vivo. J Am Soc Nephrol. 2004;15:3035-43 pubmed
    Gene targeting has been used to create a variety of lines of mice with Pkd1 mutations that share many common features. Homozygous Pkd1 mutants invariably develop pancreatic and renal cysts if they survive to day 15...
  51. Kim K, Drummond I, Ibraghimov Beskrovnaya O, Klinger K, Arnaout M. Polycystin 1 is required for the structural integrity of blood vessels. Proc Natl Acad Sci U S A. 2000;97:1731-6 pubmed
    ..5. Kidney and pancreatic ductal cysts are present. The Pkd1-encoded protein, mouse polycystin 1, was detected in normal endothelium and the surrounding vascular smooth muscle cells...
  52. Puri S, Magenheimer B, Maser R, Ryan E, Zien C, Walker D, et al. Polycystin-1 activates the calcineurin/NFAT (nuclear factor of activated T-cells) signaling pathway. J Biol Chem. 2004;279:55455-64 pubmed
    ..has been associated with the functions of polycystin-1 (PC1) and polycystin-2 (PC2), the protein products of the PKD1 and PKD2 genes...
  53. Ahrabi A, Jouret F, Marbaix E, Delporte C, Horie S, Mulroy S, et al. Glomerular and proximal tubule cysts as early manifestations of Pkd1 deletion. Nephrol Dial Transplant. 2010;25:1067-78 pubmed publisher
    The homozygous deletion of Pkd1 in the mouse results in embryonic lethality with renal cysts and hydrops fetalis, but there is no precise data on the segmental origin of cysts and potential changes associated with polyhydramnios...
  54. Guay Woodford L. Murine models of polycystic kidney disease: molecular and therapeutic insights. Am J Physiol Renal Physiol. 2003;285:F1034-49 pubmed
  55. Boletta A, Germino G. Role of polycystins in renal tubulogenesis. Trends Cell Biol. 2003;13:484-92 pubmed
    ..Study of PKD proteins will elucidate the process of renal tubular morphogenesis and guide the development of therapies. Here, we focus on insights provided by study of the most common form of PKD, autosomal dominant PKD. ..
  56. Grimm D, Cai Y, Chauvet V, Rajendran V, Zeltner R, Geng L, et al. Polycystin-1 distribution is modulated by polycystin-2 expression in mammalian cells. J Biol Chem. 2003;278:36786-93 pubmed
    Mutations in PKD1 and PKD2, the genes that encode polycystin-1 and polycystin-2 respectively, account for almost all cases of autosomal dominant polycystic kidney disease...
  57. Ittner A, Block H, Reichel C, Varjosalo M, Gehart H, Sumara G, et al. Regulation of PTEN activity by p38?-PKD1 signaling in neutrophils confers inflammatory responses in the lung. J Exp Med. 2012;209:2229-46 pubmed publisher
    ..p38? counteracts the activity of its downstream target protein kinase D1 (PKD1) in neutrophils and myeloid-restricted inactivation of PKD1 leads to exacerbated lung inflammation...
  58. Hassane S, Claij N, Lantinga van Leeuwen I, Van Munsteren J, van Lent N, Hanemaaijer R, et al. Pathogenic sequence for dissecting aneurysm formation in a hypomorphic polycystic kidney disease 1 mouse model. Arterioscler Thromb Vasc Biol. 2007;27:2177-83 pubmed
    ..The condition is mainly caused by mutations in the PKD1 or PKD2 gene...
  59. Wu G, D AGATI V, Cai Y, Markowitz G, Park J, Reynolds D, et al. Somatic inactivation of Pkd2 results in polycystic kidney disease. Cell. 1998;93:177-88 pubmed
    ..Somatic loss of Pkd2 expression is both necessary and sufficient for renal cyst formation in ADPKD, suggesting that PKD2 occurs by a cellular recessive mechanism. ..
  60. Takiar V, Nishio S, Seo Mayer P, King J, Li H, Zhang L, et al. Activating AMP-activated protein kinase (AMPK) slows renal cystogenesis. Proc Natl Acad Sci U S A. 2011;108:2462-7 pubmed publisher
    ..Our results suggest a possible role for AMPK activation in slowing renal cystogenesis as well as the potential for therapeutic application of metformin in the context of ADPKD. ..
  61. Driscoll J, Bhalla S, Liapis H, Ibricevic A, Brody S. Autosomal dominant polycystic kidney disease is associated with an increased prevalence of radiographic bronchiectasis. Chest. 2008;133:1181-8 pubmed publisher
    ..This association suggests that patients with primary cilia-associated diseases may be at risk for airway disease. ..
  62. Distefano G, Boca M, Rowe I, Wodarczyk C, Ma L, Piontek K, et al. Polycystin-1 regulates extracellular signal-regulated kinase-dependent phosphorylation of tuberin to control cell size through mTOR and its downstream effectors S6K and 4EBP1. Mol Cell Biol. 2009;29:2359-71 pubmed publisher
    ..Polycystin-1 (PC-1), a large orphan receptor encoded by the PKD1 gene and mutated in 85% of all cases, is able to inhibit proliferation and apoptosis...