Correction for Raghavan et al., Shear stress-dependent regulation of apical endocytosis in renal proximal tubule cells mediated by primary cilia

G protein-coupled receptor kinase 4 (GRK4) is a member of the GRK family which play critical role in regulation of the function of G protein-coupled receptors. Our previous studies have shown that GRK4 not only plays a role in regulating sodium excretion in renal proximal tubule cells but also acts as a stimulator on proliferation of breast cancer cells. Uncontrolled proliferation is a characteristics of cancer cells and GRK4 is upregulated in breast cancer cells. We hypothesized that expression of GRK4 may be regulated differently in cancer and non-cancer cells. To test this hypothesis, expression of GRK4 in response to serum was compared in breast cancer cells and renal proximal tubule cells by Western analysis. In three breast cancer cell lines serum withdrawal caused rapid reduction in the levels of GRK4 which occurred as early as 15 min. GRK4 levels correlated with the concentrations of serum added to the culture media. To determine if growth factors were a critical element for maintaining GRK4 levels in the cells, EGF (10-20 ng/ml) was added to serum free medium for 24 h. There was no increase in GRK4 levels in the cells treated with EGF compared with the serum starvation control. Similarly, serum withdrawal (16 h) led to 40-80% decrease of GRK4 levels in renal proximal tubule cells even in the presence of EFG supplement. Serum feeding for 30 min after starvation dramatically increased the levels of GRK4 in both breast cancer cells and RPTC which exceeded the steady state levels. This rapid recovery of GRK4 protein do not need de novo protein synthesis because pretreatment of the cells with protein synthesis inhibitor, cycloheximide (10 μg/ml, 24 h), did not prevent this event. Expression of GRK2, another member of the GRK family, was not affected by serum starvation. Our results have shown that GRK4 is very sensitive to serum concentration in breast cancer cells as well as in RPTC. Preliminary studies suggest that rapid protein degradation rather than shutting down the protein synthesis plays a major role in this kind of GRK4 regulation. The biological significance of serum regulation of GRK4 in cancer and non-cancerous cells needs further investigation.

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Insulin Increases D5 Dopamine Receptor Expression and Function in Renal Proximal Tubule Cells From Wistar-Kyoto Rats

American Journal of Hypertension ◽

10.1038/ajh.2009.69 ◽

2009 ◽

Vol 22 (7) ◽

pp. 770-776 ◽

Cited By ~ 17

Author(s):

J. Yang ◽

Z. Cui ◽

D. He ◽

H. Ren ◽

Y. Han ◽

...

Keyword(s):

Proximal Tubule ◽

Dopamine Receptor ◽

Renal Proximal Tubule ◽

Receptor Expression ◽

Proximal Tubule Cells ◽

Wistar Kyoto Rats ◽

Tubule Cells ◽

Wistar Kyoto ◽

Renal Proximal Tubule Cells ◽

And Function

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Primary cultures of renal proximal tubule cells derived from individuals with primary hyperoxaluria

Urological Research ◽

10.1007/s00240-009-0185-5 ◽

2009 ◽

Vol 37 (3) ◽

pp. 127-132 ◽

Cited By ~ 7

Author(s):

Karen L. Price ◽

Sally-Anne Hulton ◽

William G. van’t Hoff ◽

John R. Masters ◽

Gill Rumsby

Keyword(s):

Proximal Tubule ◽

Primary Cultures ◽

Primary Hyperoxaluria ◽

Renal Proximal Tubule ◽

Proximal Tubule Cells ◽

Tubule Cells ◽

Renal Proximal Tubule Cells

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Signaling pathways utilized by PTH and dopamine to inhibit phosphate transport in mouse renal proximal tubule cells

AJP Renal Physiology ◽

10.1152/ajprenal.90426.2008 ◽

2009 ◽

Vol 296 (2) ◽

pp. F355-F361 ◽

Cited By ~ 34

Author(s):

Rochelle Cunningham ◽

Rajatsubhra Biswas ◽

Marc Brazie ◽

Deborah Steplock ◽

Shirish Shenolikar ◽

...

Keyword(s):

Proximal Tubule ◽

Signaling Pathways ◽

Phosphate Transport ◽

Inhibitory Effect ◽

Renal Proximal Tubule ◽

Proximal Tubule Cells ◽

Phosphate Cotransport ◽

Tubule Cells ◽

Renal Proximal Tubule Cells ◽

Sodium Phosphate Cotransport

The present experiments were designed to detail factors regulating phosphate transport in cultured mouse proximal tubule cells by determining the response to parathyroid hormone (PTH), dopamine, and second messenger agonists and inhibitors. Both PTH and dopamine inhibited phosphate transport by over 30%. The inhibitory effect of PTH was completely abolished in the presence of chelerythrine, a PKC inhibitor, but not by Rp-cAMP, a PKA inhibitor. By contrast, both chelerythrine and Rp-cAMP blocked the inhibitory effect of dopamine. Chelerythrine inhibited PTH-mediated cAMP accumulation but also blocked the inhibitory effect of 8-bromo-cAMP on phosphate transport. On the other hand, Rp-cAMP had no effect on the ability of DOG, a PKC activator, to inhibit phosphate transport. PD98059, an inhibitor of MAPK, had no effect on PTH- or dopamine-mediated inhibition of sodium-phosphate cotransport. Finally, compared with 8-bromo-cAMP, 8-pCPT-2′- O-Me-cAMP, an activator of EPAC, had no effect on phosphate transport. These results outline significant differences in the signaling pathways utilized by PTH and dopamine to inhibit renal phosphate transport. Our results also suggest that activation of MAPK is not critically involved in PTH- or dopamine-mediated inhibition of phosphate transport in mouse renal proximal tubule cells in culture.

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