<?xml version="1.0" encoding="UTF-8"?>
<Pathway xmlns="http://pathvisio.org/GPML/2013a" Name="Na/K-ATPase/Src signaling" Data-Source="WikiPathways" Version="WP5051_r139768" Author="[Tianjiang, Eweitz, Khanspers, Ddigles]" Last-Modified="20250704141244" Organism="Mus musculus">
  <Comment Source="WikiPathways-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.</Comment>
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  <BiopaxRef>b1f</BiopaxRef>
  <BiopaxRef>cdc</BiopaxRef>
  <BiopaxRef>fa9</BiopaxRef>
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  <BiopaxRef>d5d</BiopaxRef>
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    <Comment Source="GenMAPP remarks">CAV3; caveolin 3</Comment>
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    <Comment Source="GenMAPP remarks">SEPP1; selenoprotein P  plasma</Comment>
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    <Comment Source="GenMAPP remarks">GRB2; growth factor receptor-bound protein 2</Comment>
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    <Comment Source="GenMAPP remarks">RAF1; v-raf-1 murine leukemia viral oncogene homolog 1 [EC:2.7.1.-]</Comment>
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    <Comment Source="GenMAPP remarks">ILK; integrin-linked kinase [EC:2.7.1.-]</Comment>
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    <Comment Source="GenMAPP remarks">MAPK6; mitogen-activated protein kinase 6 [EC:2.7.1.-]</Comment>
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    <Comment Source="GenMAPP remarks">DOCK1; dedicator of cyto-kinesis</Comment>
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    <Comment Source="GenMAPP remarks">ARAF1; v-raf murine sarcoma 3611 viral oncogene homolog 1 [EC:2.7.1.-]</Comment>
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    <Comment Source="GenMAPP remarks">MAP2K2; mitogen-activated protein kinase kinase 2 [EC:2.7.1.-]</Comment>
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    <Comment Source="GenMAPP remarks">MAP2K3; mitogen-activated protein kinase kinase 3 [EC:2.7.1.-]</Comment>
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    <Comment Source="GenMAPP remarks">BRAF; v-raf murine sarcoma viral oncogene homolog B1 [EC:2.7.1.-]</Comment>
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    <Comment Source="GenMAPP remarks">MAPK1; mitogen-activated protein kinase 1 [EC:2.7.1.-]</Comment>
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    <Comment Source="GenMAPP remarks">PTK2; PTK2 protein tyrosine kinase 2 [EC:2.7.1.112</Comment>
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    <Comment Source="GenMAPP remarks">MAP2K5; mitogen-activated protein kinase kinase 5 [EC:2.7.1.-]</Comment>
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