Na/K-ATPase/Src signaling (Mus musculus)

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1-17+p+p-p+pRAF+p+pMitochondriaCell Proliferation+p+p+p+pPhosphatidylinositiolsignaling systemReceptor Tyrosine KinasesOxidative StressMEK+p-p+pPIP3+p+pCell Cycle+pDNACellApoptosisCell SurvivalWnt SignalingERK+p+p+pDNADock1Mapk8Akt1CatnbHckCcnd2BrafFlt1SrmsPtk2Pik3cbBirc4FgrPak6Mapk12Rac3Ptk6Mapk1Pik3r2Akt2Map2k5EgfrPtenMapk9Casp3cycsShc1Crk1Tnk2Pak3CavSepp1Map2k6Rac1Sos1Shc3Erbb2ArafIlkMtorCcnd1Ha-RasPak1BrafRap1bPik3cgRac2Birc2JunAkt3Mapk7Rapgef1CrkBcar1Tesk2Pak4Raf1TxkBcl2Apaf1Cav2PdgfraMap2k1PdgfrbBlkIgf1rAtp1b1Pik3r4Grb2Mapk6FynPik3r1SrcPak2Casp9Pik3caBadPik3cdTnk1Birc3MetVav1Rap1aPak7Map2k3Map2k2Styk1Cav3Ccnd3Elk1Atp1a1Pik3r5Mapk4cyctKdrGsk3bROS


Description

The Na/K-ATPase, or Na+ pump, is a member of the P-type ATPase superfamily. In addition to pumping ions, Na/K-ATPase is engaged in assembly of multiple protein complexes that transmit signals to different intracellular compartments. The signaling function of the enzyme appears to have been acquired through the evolutionary incorporation of many specific binding motifs that interact with proteins and ligands. In some cell types the signaling Na/K-ATPase and its protein partners are compartmentalized in caveolae. Na/K-ATPase can bind with Src kinase and keep it inactive. However, binding of ouabain or other digitalis compound to Na/K-ATPase activates the cytoplasmic tyrosine kinase Src, resulting in the formation of an active "binary receptor" that phosphorylates and assembles other proteins into different signaling modules. This in turn activates multiple protein kinase cascades including mitogen-activated protein kinases and protein kinase C isozymes in a cell-specific manner. It also increases mitochondrial production of reactive oxygen species (ROS)and regulates intracellular calcium concentration. Crosstalk among the activated pathways eventually results in changes in the expression of a number of genes. Part of the pathway was adopted and edited from wikipathway WP85.

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Bibliography

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  1. Nicholson KM, Anderson NG; ''The protein kinase B/Akt signalling pathway in human malignancy.''; Cell Signal, 2002 PubMed Europe PMC Scholia
  2. Liu J, Nie Y, Chaudhry M, Bai F, Chuang J, Sodhi K, Shapiro JI; ''The Redox-Sensitive Na/K-ATPase Signaling in Uremic Cardiomyopathy.''; Int J Mol Sci, 2020 PubMed Europe PMC Scholia
  3. Sodhi K, Denvir J, Liu J, Sanabria JR, Chen Y, Silverstein R, Xie Z, Abraham NG, Shapiro JI; ''Oxidant-Induced Alterations in the Adipocyte Transcriptome: Role of the Na,K-ATPase Oxidant Amplification Loop.''; Int J Mol Sci, 2020 PubMed Europe PMC Scholia
  4. Oloumi A, McPhee T, Dedhar S; ''Regulation of E-cadherin expression and beta-catenin/Tcf transcriptional activity by the integrin-linked kinase.''; Biochim Biophys Acta, 2004 PubMed Europe PMC Scholia
  5. Vanhaesebroeck B, Alessi DR; ''The PI3K-PDK1 connection: more than just a road to PKB.''; Biochem J, 2000 PubMed Europe PMC Scholia
  6. Danen EH, Yamada KM; ''Fibronectin, integrins, and growth control.''; J Cell Physiol, 2001 PubMed Europe PMC Scholia
  7. Stupack DG, Cheresh DA; ''Get a ligand, get a life: integrins, signaling and cell survival.''; J Cell Sci, 2002 PubMed Europe PMC Scholia
  8. Comoglio PM, Boccaccio C, Trusolino L; ''Interactions between growth factor receptors and adhesion molecules: breaking the rules.''; Curr Opin Cell Biol, 2003 PubMed Europe PMC Scholia
  9. Yan Y, Shapiro AP, Haller S, Katragadda V, Liu L, Tian J, Basrur V, Malhotra D, Xie ZJ, Abraham NG, Shapiro JI, Liu J; ''Involvement of reactive oxygen species in a feed-forward mechanism of Na/K-ATPase-mediated signaling transduction.''; J Biol Chem, 2013 PubMed Europe PMC Scholia
  10. Liu C, Bai Y, Chen Y, Wang Y, Sottejeau Y, Liu L, Li X, Lingrel JB, Malhotra D, Cooper CJ, Shapiro JI, Xie ZJ, Tian J; ''Reduction of Na/K-ATPase potentiates marinobufagenin-induced cardiac dysfunction and myocyte apoptosis.''; J Biol Chem, 2012 PubMed Europe PMC Scholia
  11. Xie Z, Cai T; ''Na+-K+--ATPase-mediated signal transduction: from protein interaction to cellular function.''; Mol Interv, 2003 PubMed Europe PMC Scholia
  12. Lee JW, Juliano R; ''Mitogenic signal transduction by integrin- and growth factor receptor-mediated pathways.''; Mol Cells, 2004 PubMed Europe PMC Scholia
  13. Hlobilková A, Knillová J, Bártek J, Lukás J, Kolár Z; ''The mechanism of action of the tumour suppressor gene PTEN.''; Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 2003 PubMed Europe PMC Scholia
  14. Tian J, Cai T, Yuan Z, Wang H, Liu L, Haas M, Maksimova E, Huang XY, Xie ZJ; ''Binding of Src to Na+/K+-ATPase forms a functionalsignaling complex.''; Mol Biol Cell, 2006 PubMed Europe PMC Scholia
  15. Sodhi K, Srikanthan K, Goguet-Rubio P, Nichols A, Mallick A, Nawab A, Martin R, Shah PT, Chaudhry M, Sigdel S, El-Hamdani M, Liu J, Xie Z, Abraham NG, Shapiro JI; ''pNaKtide Attenuates Steatohepatitis and Atherosclerosis by Blocking Na/K-ATPase/ROS Amplification in C57Bl6 and ApoE Knockout Mice Fed a Western Diet.''; Sci Rep, 2017 PubMed Europe PMC Scholia
  16. Schmitz AA, Govek EE, Böttner B, Van Aelst L; ''Rho GTPases: signaling, migration, and invasion.''; Exp Cell Res, 2000 PubMed Europe PMC Scholia
  17. Burridge K, Wennerberg K; ''Rho and Rac take center stage.''; Cell, 2004 PubMed Europe PMC Scholia

History

CompareRevisionActionTimeUserComment
116709view09:40, 11 May 2021EweitzModified title
115160view15:38, 1 February 2021Tianjiangchange the gene symbol of mTOR to Mtor for consistency
115155view14:28, 29 January 2021TianjiangNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
Akt1GeneProduct11651 (Entrez Gene)
Akt2GeneProduct11652 (Entrez Gene)
Akt3GeneProduct23797 (Entrez Gene)
Apaf1GeneProduct11783 (Entrez Gene)
ArafGeneProduct11836 (Entrez Gene) ARAF1; v-raf murine sarcoma 3611 viral oncogene homolog 1 [EC:2.7.1.-]
Atp1a1GeneProduct11928 (Entrez Gene)
Atp1b1GeneProduct11931 (Entrez Gene)
BadGeneProduct12015 (Entrez Gene)
Bcar1GeneProduct12927 (Entrez Gene)
Bcl2GeneProduct12043 (Entrez Gene)
Birc2GeneProduct11797 (Entrez Gene)
Birc3GeneProduct11796 (Entrez Gene)
Birc4GeneProduct
BlkGeneProduct12143 (Entrez Gene)
BrafGeneProduct109880 (Entrez Gene)
Casp3GeneProduct12367 (Entrez Gene)
Casp9GeneProduct12371 (Entrez Gene)
CatnbGeneProduct
CavGeneProduct12389 (Entrez Gene) CAV1; caveolin 1 caveolae protein 22kD
Cav2GeneProduct12390 (Entrez Gene) CAV2; caveolin 2
Cav3GeneProduct12391 (Entrez Gene) CAV3; caveolin 3
Ccnd1GeneProduct12443 (Entrez Gene)
Ccnd2GeneProduct12444 (Entrez Gene)
Ccnd3GeneProduct12445 (Entrez Gene)
Crk1GeneProduct12929 (Entrez Gene)
CrkGeneProduct12928 (Entrez Gene)
Dock1GeneProductMGI:2429765 (MGI) DOCK1; dedicator of cyto-kinesis
EgfrGeneProduct13649 (Entrez Gene)
Elk1GeneProduct13712 (Entrez Gene)
Erbb2GeneProduct13866 (Entrez Gene)
FgrGeneProduct14191 (Entrez Gene)
Flt1GeneProduct14254 (Entrez Gene)
FynGeneProduct14360 (Entrez Gene) FYN; FYN oncogene related to SRC FGR YES [EC:2.7.1.112]
Grb2GeneProduct14784 (Entrez Gene) GRB2; growth factor receptor-bound protein 2
Gsk3bGeneProduct56637 (Entrez Gene)
Ha-RasGeneProduct
HckGeneProduct15162 (Entrez Gene)
Igf1rGeneProduct
IlkGeneProduct16202 (Entrez Gene) ILK; integrin-linked kinase [EC:2.7.1.-]
JunGeneProduct16476 (Entrez Gene)
KdrGeneProduct
Map2k1GeneProduct26395 (Entrez Gene) MAP2K1; mitogen-activated protein kinase kinase 1 [EC:2.7.1.-]
Map2k2GeneProduct26396 (Entrez Gene) MAP2K2; mitogen-activated protein kinase kinase 2 [EC:2.7.1.-]
Map2k3GeneProduct26397 (Entrez Gene) MAP2K3; mitogen-activated protein kinase kinase 3 [EC:2.7.1.-]
Map2k5GeneProduct23938 (Entrez Gene) MAP2K5; mitogen-activated protein kinase kinase 5 [EC:2.7.1.-]
Map2k6GeneProduct26399 (Entrez Gene) MAP2K6; mitogen-activated protein kinase kinase 6 [EC:2.7.1.-
Mapk12GeneProduct29857 (Entrez Gene) MAPK12; mitogen-activated protein kinase 12 [EC:2.7.1.-]
Mapk1GeneProduct26413 (Entrez Gene) MAPK1; mitogen-activated protein kinase 1 [EC:2.7.1.-]
Mapk4GeneProduct225724 (Entrez Gene) MAPK4; mitogen-activated protein kinase 4 [EC:2.7.1.-]
Mapk6GeneProduct50772 (Entrez Gene) MAPK6; mitogen-activated protein kinase 6 [EC:2.7.1.-]
Mapk7GeneProduct23939 (Entrez Gene) MAPK7; mitogen-activated protein kinase 7 [EC:2.7.1.-
Mapk8GeneProduct26419 (Entrez Gene)
Mapk9GeneProduct26420 (Entrez Gene)
MetGeneProduct17295 (Entrez Gene)
MtorGeneProduct56717 (Entrez Gene)
Pak1GeneProduct18479 (Entrez Gene)
Pak2GeneProduct224105 (Entrez Gene)
Pak3GeneProduct18481 (Entrez Gene)
Pak4GeneProduct70584 (Entrez Gene)
Pak6GeneProduct214230 (Entrez Gene)
Pak7GeneProduct241656 (Entrez Gene)
PdgfraGeneProduct18595 (Entrez Gene)
PdgfrbGeneProduct18596 (Entrez Gene)
Pik3caGeneProduct18706 (Entrez Gene)
Pik3cbGeneProduct74769 (Entrez Gene)
Pik3cdGeneProduct18707 (Entrez Gene)
Pik3cgGeneProduct30955 (Entrez Gene)
Pik3r1GeneProduct18708 (Entrez Gene)
Pik3r2GeneProduct18709 (Entrez Gene)
Pik3r4GeneProduct75669 (Entrez Gene)
Pik3r5GeneProduct320207 (Entrez Gene)
PtenGeneProduct19211 (Entrez Gene)
Ptk2GeneProduct14083 (Entrez Gene) PTK2; PTK2 protein tyrosine kinase 2 [EC:2.7.1.112
Ptk6GeneProduct20459 (Entrez Gene)
Rac1GeneProduct19353 (Entrez Gene)
Rac2GeneProduct19354 (Entrez Gene)
Rac3GeneProduct170758 (Entrez Gene)
Raf1GeneProductMGI:97847 (MGI) RAF1; v-raf-1 murine leukemia viral oncogene homolog 1 [EC:2.7.1.-]
Rap1aGeneProduct109905 (Entrez Gene) RAP1A; RAP1A member of RAS oncogene family
Rap1bGeneProduct215449 (Entrez Gene) RAP1B; RAP1B member of RAS oncogene family
Rapgef1GeneProduct107746 (Entrez Gene)
Sepp1GeneProduct20363 (Entrez Gene) SEPP1; selenoprotein P plasma
Shc1GeneProduct20416 (Entrez Gene) SHC1; SHC (Src homology 2 domain containing) transforming protein 1
Shc3GeneProduct20418 (Entrez Gene) SHC3; neuronal Sh
Sos1GeneProduct20662 (Entrez Gene) SOS1; son of sevenless homolog 1 (Drosophila)
SrcGeneProduct20779 (Entrez Gene) SRC; v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) [EC:2.7.1.112]
SrmsGeneProduct20811 (Entrez Gene)
Styk1GeneProduct243659 (Entrez Gene)
Tesk2GeneProduct230661 (Entrez Gene)
Tnk1GeneProduct83813 (Entrez Gene)
Tnk2GeneProduct51789 (Entrez Gene)
TxkGeneProduct22165 (Entrez Gene)
Vav1GeneProduct22324 (Entrez Gene)
cycsGeneProduct13063 (Entrez Gene)
cyctGeneProduct13067 (Entrez Gene)

Annotated Interactions

No annotated interactions

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