Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin II (ANG II) receptors of the AT1 subtype are present on the apical and basolateral membranes of renal proximal tubule cells. Cells of the proximal tubulelike cell line, LLC-PK1/Cl4, were transfected with an expression plasmid containing cDNA encoding the rabbit AT1 ANG II receptor. In transfected cells, specific binding of 125I-ANG II was detected on both apical and basolateral membranes; wild-type LLC-PK1/Cl4 cells did not express ANG II receptors. In transfected cells, apical or basolateral ANG II increased both S6 kinase activity and incorporation of [3H]leucine. In cells pretreated with pertussis toxin, the stimulatory effect of apical or basolateral ANG II on [3H]leucine incorporation was abolished. In contrast, ANG II did not affect mitogenesis, determined by [3H]thymidine incorporation. Apical or basolateral ANG II (10(-6) M) stimulated phosphoinositide turnover by 13.4 +/- 4.4% (n = 8) and 16.3 +/- 4.2% (n = 9), respectively. The activity of protein kinase C, determined by phosphorylation of a specific protein kinase C peptide substrate, was also stimulated by ANG II in transfected cells. Apical or basolateral ANG II had no significant effect on cellular adenosine 3',5'-cyclic monophosphate levels. In permeabilized transfected cells, apical ANG II (10(-6) M) inhibited the phosphorylation of a specific peptide substrate of protein kinase A; lower apical concentrations or basolateral ANG II were without significant effect. These results indicate that AT1 ANG II receptors sort to both apical and basolateral membranes in renal epithelial cells and are coupled to activation of phospholipase C. ANG II stimulates protein synthesis by binding to either apical or basolateral receptors; this effect requires coupling to G proteins and may be mediated by activation of S6 kinase. Because high concentrations of ANG II exist in proximal tubule, binding to apical and basolateral receptors may regulate proximal tubule cell growth under physiological conditions.
...
PMID:Signaling and growth responses of LLC-PK1/Cl4 cells transfected with the rabbit AT1 ANG II receptor. 773 40

The adrenergic system is important in regulating proximal tubule sodium reabsorption. Although alpha-adrenergic receptors have been identified in proximal tubules, the presence and function of beta-adrenergic receptors (BAR) in proximal tubules is less certain. The purpose of our study was to determine whether functional BAR are present on apical or basolateral surfaces of proximal tubule epithelial cells (PTEC) of rat kidney. We specifically focused on BAR coupling to adenylate cyclase and on differences between requirements for apical and basolateral receptor coupling to adenylate cyclase. To determine BAR expression and function, primary cultures of rat PTECs were grown on permeable supports. Scatchard analysis of 125I-labeled cyanopindolol binding revealed a single class of receptors on both apical and basolateral surfaces. Apical isoproterenol (ISO) resulted in time- and concentration-dependent increases in adenosine 3',5'-cyclic monophosphate (cAMP) that were 50% of responses after basolateral ISO. Apical BAR-cAMP coupling was mediated by B1-adrenergic receptors (B1AR), since apical cAMP responses were abrogated with apical (but not basolateral) B1 but not B2 antagonists. Apical B1AR required endocytosis prior to adenylate cyclase activation, since increases in cAMP were prevented by phenylarsine oxide or colchicine. B1AR-adenylate cyclase coupling was independent of intra- or extracellular calcium, cyclooxygenase metabolites, and protein kinase C (PKC) and dependent on Gs guanine nucleotide regulatory protein. Prolonged exposure to ISO resulted in time- and concentration-dependent homologous desensitization of cAMP responses. Desensitization was independent of receptor sequestration, PKA, or PKC. We conclude the following: B1AR are present on both apical and basolateral surfaces of rat PTECs.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Beta-adrenergic receptor function in rat proximal tubule epithelial cells in culture. 773 11

Activation of cAMP-dependent protein kinase A inhibits the renal proximal tubule brush border membrane Na(+)-H+ exchanger by a process involving participation of a regulatory cofactor (NHE-RF) that is distinct from the transporter itself. Recent studies from this laboratory reported a partial amino acid sequence of this putative cofactor (Weinman, E. J., D. H. Steplock, and S. Shenolikar. 1993. J. Clin. Invest. 92:1781-1786). The present experiments detail the structure of the NHE-RF protein as determined from molecular cloning studies. A codon-biased oligonucleotide probe to a portion of the amino acid sequence of the putative cofactor was used to isolate a 1.9-kb cDNA from a rabbit renal library. The encoded protein is 358 amino acids in length and is rich in proline residues. Search of existing data bases indicates that NHE-RF is a unique protein. Using a reticulocyte lysate, the cDNA translated a product of approximately 44 kD, which was recognized by an affinity-purified polyclonal antibody to NHE-RF. Potential phosphorylation sites for protein kinase A are present. The mRNA for the protein is expressed in kidney, proximal small intestine, and liver. Reverse transcription/PCR studies in the kidney indicate the presence of mRNA for NHE-RF in several distinct nephron segments including the proximal tubule.
...
PMID:Characterization of a protein cofactor that mediates protein kinase A regulation of the renal brush border membrane Na(+)-H+ exchanger. 773 82

The cellular mechanisms controlling reabsorption of amino acids in the renal proximal tubule are unknown. Ca(2+)-dependent protein kinases modulate the activity of several ion channels and carriers in the kidney. The role of these enzymes in regulating tubular amino acid transport has not been established. We investigated the effect of Ca(2+)- and phospholipid-dependent protein kinase C (PKC) and Ca2+/calmodulin-dependent protein kinase II (CaMK II) on Na(+)- and Cl(-)-dependent proline transport across the rat renal brush-border membrane (BBM). Bioassays utilizing selective peptide substrates for Ca(2+)-dependent protein kinases demonstrated the presence of PKC and CaMK II in the BBM. Renal brush-border membrane vesicles (BBMV) were phosphorylated using the "hyposmotic shock" technique. Endogenous (membrane-bound) CaMK II and PKC, as well as exogenous, highly purified PKC inhibited NaCl-linked proline uptake by phosphorylated, lysed/resealed BBMV compared with control vesicles. The inhibitory effect of Ca2+ on proline transport, without the presence of other kinase activators, was mediated by activation of endogenous CaMK II. The CaMK II- and PKC-induced inhibition of proline uptake was reversed by the specific kinase inhibitor peptides CaMK II-(281-302) and PKC-(19-31), respectively. These data suggest that Ca(2+)-dependent protein kinase-mediated phosphorylation inhibits NaCl-dependent proline transport across the tubular luminal membrane.
...
PMID:Ca(2+)-dependent protein kinases modulate proline transport across the renal brush-border membrane. 784 Feb 41

Winter flounder renal proximal tubule primary monolayer cultures mounted in Ussing chambers were used to determine the effect of salmon somatolactin (sSL) on transepithelial Pi and Ca2+ transport. sSL stimulated Pi reabsorption in a dose-dependent manner at physiological levels of the hormone (12.5 ng/ml). Net Pi transport was significantly altered by sSL (200 ng/ml) within 2 h after the initial exposure. Ca2+ fluxes were unchanged by the addition of 200 ng/ml sSL. The sSL-induced Pi reabsorption was abolished by 10 microM H-89, a highly specific protein kinase A inhibitor. Moreover the production and release of adenosine 3',5'-cyclic monophosphate were significantly increased after 1 and 2 h of exposure to sSL. The data indicate that sSL directly stimulates net renal Pi reabsorption by an adenosine 3',5'-cyclic monophosphate-dependent pathway. In addition to sSL, flounder SL and rat prolactin greatly, and salmon growth hormone (2.3 micrograms/ml) slightly, increased net Pi reabsorptive flux, whereas salmon prolactin had no effect.
...
PMID:Effect of somatolactin and related hormones on phosphate transport by flounder renal tubule primary cultures. 790 Aug 98

The effects of several hormones on transepithelial Pi transport were determined in primary monolayer cultures of winter flounder proximal tubule epithelium in Ussing chambers. Salmon stanniocalcin (STC) had a dose-dependent stimulatory effect on net Pi reabsorption within the normal plasma hormone concentration range, 12.5-50 ng/ml (0.25-1.0 nM). Net Pi transport was significantly altered by STC (200 ng/ml) within 30 min and progressively increased from slight net secretion (0.26 +/- 0.744 nmol.cm-2.h-1) in untreated controls to net reabsorption (1.96 +/- 0.729 nmol.cm-2.h-1) after 3 h. The STC effect was mimicked by 10 microM forskolin, whereas 10 microM H-89, a highly specific protein kinase A inhibitor, significantly decreased both STC- and forskolin-induced Pi reabsorption. The release of adenosine 3',5'-cyclic monophosphate (cAMP) was increased more than twofold after a 1-h exposure to STC. This hormone had no effect on transepithelial Ca2+ transport. The results indicate that STC directly stimulates net renal Pi reabsorption by a cAMP-dependent pathway. In addition to STC, bovine parathyroid hormone (100 nM) and ovine prolactin (100 nM) significantly increased net Pi reabsorptive flux.
...
PMID:Stanniocalcin stimulates phosphate reabsorption by flounder renal proximal tubule in primary culture. 797 65

To study signaling pathways regulated by alpha s and alpha i1 in renal epithelial cells, we expressed mutant, activated forms of alpha s and alpha i1 in a continuous proximal tubule cell line (MCT cells). alpha sQ227L increased cAMP production, and alpha ilQ204L reduced forskolin-sensitive cAMP production. alpha ilQ204L increased and alpha sQ227L decreased bradykinin-induced Ca influx across the cell membrane, but neither mutant affected bradykinin-stimulated intracellular Ca release or basal Ca influx. Bradykinin-stimulated Ca influx was reduced by dibutyryl cAMP, isoproterenol, and forskolin. Expression of a mutant regulatory type I subunit for cAMP-dependent protein kinase with reduced affinity for cAMP and treatment with KT-5720, a specific cAMP-dependent protein kinase inhibitor, enhanced Ca influx to a degree similar to that in cells expressing alpha ilQ204L. Bradykinin-stimulated c-fos mRNA expression is partially dependent on extracellular Ca. alpha sQ227L reduced and alpha ilQ204L enhanced bradykinin-stimulated c-fos expression. Consequently, in bradykinin-stimulated cells, the adenylyl cyclase system regulates Ca influx through cAMP-dependent protein kinase, but not intracellular Ca release. Furthermore, the Ca influx mechanism acts as an integrator of two signaling pathways such that Ca-dependent signals are damped by activators of adenylyl cyclase and enhanced by inhibitors of adenylyl cyclase.
...
PMID:Regulation of hormone-sensitive calcium influx by the adenylyl cyclase system in renal epithelial cells. 804 Feb 74

The renal basolateral Na+/HCO3- cotransporter is the main system responsible for HCO3- transport from proximal tubule cells into the blood. The present study was aimed at purifying and functionally reconstituting the Na+/HCO3- cotransporter protein from rabbit renal cortex. Highly purified rabbit renal cortical basolateral membrane vesicles (hereafter designated as original basolateral membrane), enriched 12-fold in Na-K-ATPase, were solubilized in 2% octylglucoside, and then reconstituted in L-alpha-phosphatidylcholine (proteoliposomes). Na+/HCO3- cotransporter activity was assessed as the difference in 22Na uptake in the presence of HCO3- and gluconate. The activity of the Na+/HCO3- cotransporter was enhanced 18-fold in the solubilized protein reconstituted into proteoliposomes compared to the original basolateral membranes. The reconstituted solubilized purified protein exhibited kinetic properties similar to the cotransporter from original basolateral membranes. In addition, it was like the original cotransporter, inhibited by disulfonic stilbene SITS, and was electrogenic. The catalytic subunit of protein kinase A significantly inhibited Na+/HCO3- cotransporter activity in proteoliposomes. The octylglucoside-solubilized protein was further purified by hydroxylapatite column chromatography, and this resulted in an additional enhancement of Na+/HCO3- cotransporter activity of 80-fold over the original basolateral membranes. The fractions containing the highest activity were further processed by glycerol gradient centrifugation, resulting in a 124- to 300-fold increase in Na+/HCO3- cotransporter activity compared to the original basolateral membranes. SDS-PAGE analysis showed an enhancement of a protein doublet of 56 kD MW in the glycerol gradient fraction. Our results demonstrate that we have partially purified and reconstituted the renal Na+/HCO3- cotransporter and suggest that the 56 kD doublet protein may represent the Na+/HCO3- cotransporter.
...
PMID:Renal cortical basolateral Na+/HCO3- cotransporter: I. Partial purification and reconstitution. 805 91

The second-messengers cAMP, diacylglycerol and inositol 1,4,5-trisphosphate (IP3)-Ca2+ ([Ca2+]i) have been implicated in parathyroid hormone (PTH) receptor-mediated inhibition of sodium/phosphate (Na/P(i)) cotransport across the apical membrane of the proximal tubule. Studies on opossum kidney (OK) cells have been used to study regulatory cascades involved in these PTH actions. In the present study, we further characterized PTH regulatory pathways in two stable mutant cell sublines (J01 and J141) compared to control OK (J09) cells. In J09 cells, addition of PTH resulted in a dose-dependent decrease in Na/P(i) uptake which was associated with an increase in cAMP and cytosolic Ca2+ concentration as well as with activation of protein kinase A, protein kinase C, and MAP kinase. Activation of protein kinase C and of MAP kinase can be detected at PTH concentrations lower than those required for protein kinase A activity. PTH led to similar changes in J01 cells except for the absence of PTH-induced Ca2+ transients. These data confirm the important role of protein kinase C and suggest further that [Ca2+]i transients are not necessary for PTH-mediated inhibition of Na/P(i) cotransport. The J141 subline possessed all of the measured PTH signal pathways but PTH was without effect on Na/P(i) cotransport. The absence of PTH response on Na/P(i) cotransport in J141 cells is likely beyond the PTH-dependent activation of protein kinase A and/or protein kinase C. These studies suggest that Na/P(i) cotransport may be uncoupled from the normal regulatory process. These defined OK cell sublines may be useful in further characterization of PTH action on Na/P(i) cotransport.
...
PMID:Abnormalities of parathyroid hormone-mediated signal transduction mechanisms in opossum kidney cells. 806 Oct 43

Calcitonin (CT), which regulates serum calcium through its actions in bone and the kidney tubule, also has a potent natriuretic effect in vivo. Na reabsorption in the proximal kidney tubule is mostly dependent on the activity of the Na,K-ATPase and the apical Na/H exchanger. We have previously shown that CT regulates the activity of the Na,K-ATPase in the proximal kidney tubule cell line LLC-PK1 in a cell cycle-dependent manner. We report here that, in the same cells, CT also regulates the Na/H exchanger through a cell cycle-specific activation of the Ca/calmodulin-dependent protein kinase II. In G2 phase, no changes in ethylisopropyl amiloride-sensitive 22Na uptake is observed, despite an increase in cAMP. In contrast, the hormone inhibits the apical exchanger when the cells are in S phase, resulting in an 80% inhibition of 22Na uptake. These results demonstrate that CT affects the activity of the two major proximal tubule Na transport systems and may help clarify the mechanisms by which CT regulates Na+ reabsorption.
...
PMID:Cell cycle-dependent and kinase-specific regulation of the apical Na/H exchanger and the Na,K-ATPase in the kidney cell line LLC-PK1 by calcitonin. 813 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---