Phosphoinositide-3 kinase binds to a proline-rich motif in the Na
            <sup>+</sup>
            ,K
            <sup>+</sup>
            -ATPase α subunit and regulates its trafficking

Yudowski, Guillermo A.; Efendiev, Riad; Pedemonte, Carlos H.; Katz, Adrian I.; Berggren, Per Olof; Bertorello, Alejandro M.

doi:10.1073/pnas.100128297

Cited by 161 publications

(127 citation statements)

References 52 publications

(58 reference statements)

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“…Binding of TCTP to the a1 subunit of Na,K-ATPase induces the release and activation of Src Recent studies suggest that phosphatidylinositol 3-kinase (PI3K) binds to the N-terminal proline-rich motif of Na,K-ATPase a subunit and that partial inhibition of Na,K-ATPase by ouabain induces Src binding to the Na,K-ATPase a subunit (Yudowski et al, 2000;Tian et al, 2006). We found that TCTP bound to the Na, K-ATPase a subunit partially inhibits its pumping activity (Jung et al, 2004).…”

Section: Resultsmentioning

confidence: 99%

Translationally controlled tumor protein induces human breast epithelial cell transformation through the activation of Src

et al. 2011

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Translationally controlled tumor protein (TCTP) is implicated in cell growth and malignant transformation. TCTP has been found to interact directly with the third cytoplasmic domain of the a subunit of Na,K-ATPase, but whether this interaction has a role in tumorigenesis is unclear. In this study, we examined TCTP-induced tumor progression signaling networks in human breast epithelial cells, using adenoviral infection. We found that TCTP (a) induces Src release from Na,K-ATPase a subunit and Src activation; (b) phosphorylates tyrosine residues 845, 992, 1086, 1148 and 1173 on anti-epidermal growth factor receptor (EGFR); (c) activates PI3K (phosphatidylinositol 3-kinase )-AKT, Ras-Raf-MEK-ERK1/2, Rac-PAK1/ 2, MKK3/6-p38 and phospholipase C (PLC)-c pathways; (d) enhances NADPH oxidase-dependent reactive oxygen species (ROS) generation; (e) stimulates cytoskeletal remodeling and cell motility and (f) upregulates matrix metalloproteinase (MMP) 3 and 13. These findings suggest that TCTP induces tumorigenesis through distinct multicellular signaling pathways involving Src-dependent EGFR transactivation, ROS generation and MMP expression.

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Section: Resultsmentioning

confidence: 99%

Translationally controlled tumor protein induces human breast epithelial cell transformation through the activation of Src

et al. 2011

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“…Interestingly, the p85 subunit of PI3 kinase can also directly interact with the Na + /K + ATPase (Chibalin et al 1998;Yudowski et al 2000). Adaptin binds to cargo proteins, recruits clathrin and promotes the formation of clathrin-coated pits (Kirchhausen 2000), triggering an endocytotic process of the Na + /K + ATPase that reduces sodium pump activity in the kidney and causes a decreased Na + reabsorption upon dopamine stimulation.…”

Section: Polymorphisms In Adducin Genesmentioning

confidence: 99%

Genetics of arterial hypertension and hypotension

Rosskopf

Schürks

Rimmbach

et al. 2007

Naunyn-Schmied Arch Pharmacol

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Human hypertension affects affects more than 20% of the adult population in industrialized countries, and it is implicated in millions of deaths worldwide each year from stroke, heart failure and ischemic heart disease. Available evidence suggests a major genetic impact on blood pressure regulation. Studies in monogenic hypertension revealed that renal salt and volume regulation systems are predominantly involved in the genesis of these disorders. Mutations here affect the synthesis of mineralocorticoids, the function of the mineralocorticoid receptor, epithelial sodium channels and their regulation by a new class of kinases, termed WNK kinases. It has been learned from monogenic hypotension that almost all ion transporters involved in the renal uptake of Na + have a major impact on blood pressure regulation. For essential hypertension as a complex disease, many candidate genes have been analysed. These include components of the reninangiotensin-aldosterone system, adducin, β-adrenoceptors, G protein subunits, regulators of G protein signalling (RGS) proteins, Rho kinases and G protein receptor kinases. At present, the individual impact of common polymorphisms in these genes on the observed blood pressure variation, on risk for stroke and as predictors of antihypertensive responses remains small and clinically irrelevant. Nevertheless, these studies have greatly augmented our knowledge on the regulation of renal functions, cellular signal transduction and the integration of both. Together, this provides the basis for the identification of novel drug targets and, hopefully, innovative antihypertensive drugs.

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“…However, phosphorylation may not affect the intrinsic properties of the Na ϩ ,K ϩ -ATPase (i.e., catalytic activity) but their subcellular distribution. For example, in renal epithelial cells inhibition of Na ϩ ,K ϩ -ATPase activity by catecholamines or phorbol esters is mediated by phosphorylation of the catalytic ␣-subunit, and this event does not affect the catalytic properties of the enzyme while in the plasma membrane but constitutes the triggering signal for its endocytosis into endosomes via a clathrin vesicle-dependent mechanism (Chibalin et al, 1997Yudowski et al, 2000;Efendiev et al, 2002). By contrast, in lung alveolar epithelial cells isoproterenol or DA increase Na ϩ , K ϩ -ATPase activity and this effect is associated with an increased recruitment of active Na ϩ , K ϩ -ATPase molecules to the plasma membrane Lecuona et al, 2000;Ridge et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Analysis of Na⁺,K⁺-ATPase Motion and Incorporation into the Plasma Membrane in Response to G Protein–coupled Receptor Signals in Living Cells

Bertorello

Komarova

Smith

et al. 2003

MBoC

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Dopamine (DA) increases Na+,K+-ATPase activity in lung alveolar epithelial cells. This effect is associated with an increase in Na+,K+-ATPase molecules within the plasma membrane ( Ridge et al., 2002 ). Analysis of Na+,K+-ATPase motion was performed in real-time in alveolar cells stably expressing Na+,K+-ATPase molecules carrying a fluorescent tag (green fluorescent protein) in the α-subunit. The data demonstrate a distinct (random walk) pattern of basal movement of Na+,K+-ATPase–containing vesicles in nontreated cells. DA increased the directional movement (by 3.5 fold) of the vesicles and an increase in their velocity (by 25%) that consequently promoted the incorporation of vesicles into the plasma membrane. The movement of Na+,K+-ATPase–containing vesicles and incorporation into the plasma membrane were microtubule dependent, and disruption of this network perturbed vesicle motion toward the plasma membrane and prevented the increase in the Na+,K+-ATPase activity induced by DA. Thus, recruitment of new Na+,K+-ATPase molecules into the plasma membrane appears to be a major mechanism by which dopamine increases total cell Na+,K+-ATPase activity.

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Phosphoinositide-3 kinase binds to a proline-rich motif in the Na ⁺ ,K ⁺ -ATPase α subunit and regulates its trafficking

Cited by 161 publications

References 52 publications

Translationally controlled tumor protein induces human breast epithelial cell transformation through the activation of Src

Translationally controlled tumor protein induces human breast epithelial cell transformation through the activation of Src

Genetics of arterial hypertension and hypotension

Analysis of Na⁺,K⁺-ATPase Motion and Incorporation into the Plasma Membrane in Response to G Protein–coupled Receptor Signals in Living Cells

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Phosphoinositide-3 kinase binds to a proline-rich motif in the Na + ,K + -ATPase α subunit and regulates its trafficking

Cited by 161 publications

References 52 publications

Translationally controlled tumor protein induces human breast epithelial cell transformation through the activation of Src

Translationally controlled tumor protein induces human breast epithelial cell transformation through the activation of Src

Genetics of arterial hypertension and hypotension

Analysis of Na+,K+-ATPase Motion and Incorporation into the Plasma Membrane in Response to G Protein–coupled Receptor Signals in Living Cells

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Product

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Phosphoinositide-3 kinase binds to a proline-rich motif in the Na ⁺ ,K ⁺ -ATPase α subunit and regulates its trafficking

Analysis of Na⁺,K⁺-ATPase Motion and Incorporation into the Plasma Membrane in Response to G Protein–coupled Receptor Signals in Living Cells