Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\27432882
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Biol+Chem
2016 ; 291
(36
): 18632-42
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Convergent Signaling Pathways Regulate Parathyroid Hormone and Fibroblast Growth
Factor-23 Action on NPT2A-mediated Phosphate Transport
#MMPMID27432882
Sneddon WB
; Ruiz GW
; Gallo LI
; Xiao K
; Zhang Q
; Rbaibi Y
; Weisz OA
; Apodaca GL
; Friedman PA
J Biol Chem
2016[Sep]; 291
(36
): 18632-42
PMID27432882
show ga
Parathyroid hormone (PTH) and FGF23 are the primary hormones regulating acute
phosphate homeostasis. Human renal proximal tubule cells (RPTECs) were used to
characterize the mechanism and signaling pathways of PTH and FGF23 on phosphate
transport and the role of the PDZ protein NHERF1 in mediating PTH and FGF23
effects. RPTECs express the NPT2A phosphate transporter, ?Klotho, FGFR1, FGFR3,
FGFR4, and the PTH receptor. FGFR1 isoforms are formed from alternate splicing of
exon 3 and of exon 8 or 9 in Ir-like loop 3. Exon 3 was absent, but mRNA
containing both exons 8 and 9 is present in cytoplasm. Using an FGFR1c-specific
antibody together with mass spectrometry analysis, we show that RPTECs express
FGFR-?1C. The data are consistent with regulated FGFR1 splicing involving a novel
cytoplasmic mechanism. PTH and FGF23 inhibited phosphate transport in a
concentration-dependent manner. At maximally effective concentrations, PTH and
FGF23 equivalently decreased phosphate uptake and were not additive, suggesting a
shared mechanism of action. Protein kinase A or C blockade prevented PTH but not
FGF23 actions. Conversely, inhibiting SGK1, blocking FGFR dimerization, or
knocking down Klotho expression disrupted FGF23 actions but did not interfere
with PTH effects. C-terminal FGF23(180-251) competitively and selectively blocked
FGF23 action without disrupting PTH effects. However, both PTH and
FGF23-sensitive phosphate transport were abolished by NHERF1 shRNA knockdown.
Extended treatment with PTH or FGF23 down-regulated NPT2A without affecting
NHERF1. We conclude that FGFR1c and PTHR signaling pathways converge on NHERF1 to
inhibit PTH- and FGF23-sensitive phosphate transport and down-regulate NPT2A.