Acute regulation of renal Na+/H+ exchanger NHE3 by dopamine: role of protein phosphatase 2A. 2010

I Alexandru Bobulescu, and Henry Quiñones, and Serge M Gisler, and Francesca Di Sole, and Ming-Chang Hu, and Mingjun Shi, and Jianning Zhang, and Daniel G Fuster, and Nancy Wright, and Marc Mumby, and Orson W Moe
Dept. of Internal Medicine, Div. of Nephrology, Univ. of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-8856, USA.

Nephrogenic dopamine is a potent natriuretic paracrine/autocrine hormone that is central for mammalian sodium homeostasis. In the renal proximal tubule, dopamine induces natriuresis partly via inhibition of the sodium/proton exchanger NHE3. The signal transduction pathways and mechanisms by which dopamine inhibits NHE3 are complex and incompletely understood. This manuscript describes the role of the serine/threonine protein phosphatase 2A (PP2A) in the regulation of NHE3 by dopamine. The PP2A regulatory subunit B56δ (coded by the Ppp2r5d gene) directly associates with more than one region of the carboxy-terminal hydrophilic putative cytoplasmic domain of NHE3 (NHE3-cyto), as demonstrated by yeast-two-hybrid, coimmunoprecipitation, blot overlay, and in vitro pull-down assays. Phosphorylated NHE3-cyto is a substrate for purified PP2A in an in vitro dephosphorylation reaction. In cultured renal cells, inhibition of PP2A by either okadaic acid or by overexpression of the simian virus 40 (SV40) small T antigen blocks the ability of dopamine to inhibit NHE3 activity and to reduce surface NHE3 protein. Dopamine-induced NHE3 redistribution is also blocked by okadaic acid ex vivo in rat kidney cortical slices. These studies demonstrate that PP2A is an integral and critical participant in the signal transduction pathway between dopamine receptor activation and NHE3 inhibition.

UI MeSH Term Description Entries
D007687 Kidney Tubules, Proximal The renal tubule portion that extends from the BOWMAN CAPSULE in the KIDNEY CORTEX into the KIDNEY MEDULLA. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the U-shaped LOOP OF HENLE. Proximal Kidney Tubule,Proximal Renal Tubule,Kidney Tubule, Proximal,Proximal Kidney Tubules,Proximal Renal Tubules,Renal Tubule, Proximal,Renal Tubules, Proximal,Tubule, Proximal Kidney,Tubule, Proximal Renal,Tubules, Proximal Kidney,Tubules, Proximal Renal
D009893 Opossums New World marsupials of the family Didelphidae. Opossums are omnivorous, largely nocturnal and arboreal MAMMALS, grow to about three feet in length, including the scaly prehensile tail, and have an abdominal pouch in which the young are carried at birth. Didelphidae,Opossum
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D000074083 Sodium-Hydrogen Exchanger 3 A sodium-hydrogen antiporter expressed primarily by EPITHELIAL CELLS in the kidneys, it localizes to the apical membrane of the PROXIMAL KIDNEY TUBULE, where it functions in sodium and water reabsorption and possibly calcium homeostasis. It also is expressed in heart, brain, and lung tissues and is resistant to AMILORIDE inhibition. NHE-3 Protein,Na(+)-H(+) Exchanger 3,SLC9A3 Protein,Solute Carrier Family 9 Member 3,NHE 3 Protein,Sodium Hydrogen Exchanger 3
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000952 Antigens, Polyomavirus Transforming Polyomavirus antigens which cause infection and cellular transformation. The large T antigen is necessary for the initiation of viral DNA synthesis, repression of transcription of the early region and is responsible in conjunction with the middle T antigen for the transformation of primary cells. Small T antigen is necessary for the completion of the productive infection cycle. Polyomavirus Large T Antigens,Polyomavirus Middle T Antigens,Polyomavirus Small T Antigens,Polyomavirus T Proteins,Polyomavirus Transforming Antigens,Polyomavirus Tumor Antigens,SV40 T Antigens,SV40 T Proteins,Simian Sarcoma Virus Proteins,Polyomaviruses Large T Proteins,Polyomaviruses Middle T Proteins,Polyomaviruses Small T Proteins,Antigens, Polyomavirus Tumor,Antigens, SV40 T,Proteins, Polyomavirus T,Proteins, SV40 T,T Antigens, SV40,T Proteins, Polyomavirus,T Proteins, SV40,Transforming Antigens, Polyomavirus,Tumor Antigens, Polyomavirus
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D054648 Protein Phosphatase 2 A phosphoprotein phosphatase subtype that is comprised of a catalytic subunit and two different regulatory subunits. At least two genes encode isoforms of the protein phosphatase catalytic subunit, while several isoforms of regulatory subunits exist due to the presence of multiple genes and the alternative splicing of their mRNAs. Protein phosphatase 2 acts on a broad variety of cellular proteins and may play a role as a regulator of intracellular signaling processes. PPP2CA Phosphatase,PPP2CB Phosphatase,Protein Phosphatase 2, Catalytic Subunit,Protein Phosphatase 2, Catalytic Subunit, alpha Isoform,Protein Phosphatase 2, Catalytic Subunit, beta Isoform,Protein Phosphatase 2, Regulatory Subunit,Protein Phosphatase 2, Regulatory Subunit A, alpha Isoform,Protein Phosphatase 2, Regulatory Subunit A, beta Isoform,Protein Phosphatase 2, Regulatory Subunit B, alpha Isoform,Protein Phosphatase 2, Regulatory Subunit B, beta Isoform,Protein Phosphatase 2, Regulatory Subunit B, delta Isoform,Protein Phosphatase 2, Regulatory Subunit B, gamma Isoform,Protein Phosphatase 2A, Catalytic Subunit, alpha Isoform,Protein Phosphatase 2A, Catalytic Subunit, beta Isoform,Protein Phosphatase 2A, Regulatory Subunit A , alpha Isoform,Protein Phosphatase 2A, Regulatory Subunit A, beta Isoform,Protein Phosphatase 2A, Regulatory Subunit B, alpha Isoform,Protein Phosphatase 2A, Regulatory Subunit B, beta Isoform,Protein Phosphatase 2A, Regulatory Subunit B, delta Isoform,Protein Phosphatase 2A, Regulatory Subunit B, gamma Isoform,Protein Phosphatase-2A,Serine Threonine Protein Phosphatase 2A Catalytic Subunit beta Isoform,Serine-Threonine-Protein Phosphatase 2A Catalytic Subunit alpha Isoform,Phosphatase, PPP2CA,Phosphatase, PPP2CB,Protein Phosphatase 2A,Serine Threonine Protein Phosphatase 2A Catalytic Subunit alpha Isoform

Related Publications

I Alexandru Bobulescu, and Henry Quiñones, and Serge M Gisler, and Francesca Di Sole, and Ming-Chang Hu, and Mingjun Shi, and Jianning Zhang, and Daniel G Fuster, and Nancy Wright, and Marc Mumby, and Orson W Moe
May 1999, The American journal of physiology,
I Alexandru Bobulescu, and Henry Quiñones, and Serge M Gisler, and Francesca Di Sole, and Ming-Chang Hu, and Mingjun Shi, and Jianning Zhang, and Daniel G Fuster, and Nancy Wright, and Marc Mumby, and Orson W Moe
May 2013, American journal of physiology. Renal physiology,
I Alexandru Bobulescu, and Henry Quiñones, and Serge M Gisler, and Francesca Di Sole, and Ming-Chang Hu, and Mingjun Shi, and Jianning Zhang, and Daniel G Fuster, and Nancy Wright, and Marc Mumby, and Orson W Moe
February 2007, American journal of physiology. Renal physiology,
I Alexandru Bobulescu, and Henry Quiñones, and Serge M Gisler, and Francesca Di Sole, and Ming-Chang Hu, and Mingjun Shi, and Jianning Zhang, and Daniel G Fuster, and Nancy Wright, and Marc Mumby, and Orson W Moe
January 2002, Nephrologie,
I Alexandru Bobulescu, and Henry Quiñones, and Serge M Gisler, and Francesca Di Sole, and Ming-Chang Hu, and Mingjun Shi, and Jianning Zhang, and Daniel G Fuster, and Nancy Wright, and Marc Mumby, and Orson W Moe
December 2003, Kidney international,
I Alexandru Bobulescu, and Henry Quiñones, and Serge M Gisler, and Francesca Di Sole, and Ming-Chang Hu, and Mingjun Shi, and Jianning Zhang, and Daniel G Fuster, and Nancy Wright, and Marc Mumby, and Orson W Moe
October 2000, The Journal of biological chemistry,
I Alexandru Bobulescu, and Henry Quiñones, and Serge M Gisler, and Francesca Di Sole, and Ming-Chang Hu, and Mingjun Shi, and Jianning Zhang, and Daniel G Fuster, and Nancy Wright, and Marc Mumby, and Orson W Moe
March 2006, American journal of physiology. Cell physiology,
I Alexandru Bobulescu, and Henry Quiñones, and Serge M Gisler, and Francesca Di Sole, and Ming-Chang Hu, and Mingjun Shi, and Jianning Zhang, and Daniel G Fuster, and Nancy Wright, and Marc Mumby, and Orson W Moe
April 2005, Biochemistry,
I Alexandru Bobulescu, and Henry Quiñones, and Serge M Gisler, and Francesca Di Sole, and Ming-Chang Hu, and Mingjun Shi, and Jianning Zhang, and Daniel G Fuster, and Nancy Wright, and Marc Mumby, and Orson W Moe
January 2004, The Journal of biological chemistry,
I Alexandru Bobulescu, and Henry Quiñones, and Serge M Gisler, and Francesca Di Sole, and Ming-Chang Hu, and Mingjun Shi, and Jianning Zhang, and Daniel G Fuster, and Nancy Wright, and Marc Mumby, and Orson W Moe
October 1989, Kidney international,
Copied contents to your clipboard!