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


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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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


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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)
BlkGeneProduct12143 (Entrez Gene)
BrafGeneProduct109880 (Entrez Gene)
Casp3GeneProduct12367 (Entrez Gene)
Casp9GeneProduct12371 (Entrez Gene)
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:]
Grb2GeneProduct14784 (Entrez Gene) GRB2; growth factor receptor-bound protein 2
Gsk3bGeneProduct56637 (Entrez Gene)
HckGeneProduct15162 (Entrez Gene)
IlkGeneProduct16202 (Entrez Gene) ILK; integrin-linked kinase [EC:2.7.1.-]
JunGeneProduct16476 (Entrez Gene)
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:
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:]
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

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