|
|
||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Pediatrics, University of Arizona, Tucson, AZ, USA
* To whom correspondence should be addressed. E-mail: fghishan{at}peds.arizona.edu.
The type IIb sodium-phosphate (NaPi-IIb) cotransporter mediates intestinal phosphate absorption. Previous work in our laboratory has shown that EGF inhibited NaPi-IIb cotransporter expression through transcriptional regulation. To understand this regulation, progressively shorter hNaPi-IIb promoter constructs were used to define the EGF response region, and Gel Mobility Shift Assays (GMSAs) were used to characterize DNA-protein interactions. Promoter analysis determined that the EGF response region was located between -784 and -729 bp of the promoter. GMSAs and over-expression studies revealed an interaction between this promoter region and c-myb transcription factor. Inhibition of EGF receptor activation restored promoter function. Further studies suggested that MAPK, PKC and/or PKA pathways are involved in this regulation. In conclusion, these studies suggest that EGF decreases hNaPi-IIb gene expression by modifying the c-myb protein such that it inhibits transcriptional activation. We further conclude that this down-regulation of promoter function is mediated by EGF activated PKC/PKA and MAPK pathways. This is the first study that demonstrates the involvement of c-myb in regulation of intestinal nutrient absorption.
This article has been cited by other articles:
![]() |
F. O'Mahony, F. Toumi, M. S. Mroz, G. Ferguson, and S. J. Keely Induction of Na+/K+/2Cl- cotransporter expression mediates chronic potentiation of intestinal epithelial Cl- secretion by EGF Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1362 - C1370. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Hua, H. Xu, J. K. Uno, M. A. Lipko, J. Dong, P. R. Kiela, and F. K. Ghishan Sp1 and Sp3 mediate NHE2 gene transcription in the intestinal epithelial cells Am J Physiol Gastrointest Liver Physiol, July 1, 2007; 293(1): G146 - G153. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Marks, S. K. Srai, J. Biber, H. Murer, R. J. Unwin, and E. S. Debnam Intestinal phosphate absorption and the effect of vitamin D: a comparison of rats with mice Exp Physiol, May 1, 2006; 91(3): 531 - 537. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Xu, J. K. Uno, M. Inouye, J. F. Collins, and F. K. Ghishan NF1 transcriptional factor(s) is required for basal promoter activation of the human intestinal NaPi-IIb cotransporter gene Am J Physiol Gastrointest Liver Physiol, February 1, 2005; 288(2): G175 - G181. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |