Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 276, Issue 22, Pages 19126-19131Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M101777200
Keywords
-
Categories
Funding
- NIDDK NIH HHS [K08 DK02496] Funding Source: Medline
Ask authors/readers for more resources
Growth factors suppress the degradation of cellular proteins in lysosomes in renal epithelial cells, Whether this process also involves specific classes of proteins that influence growth processes is unknown. We investigated chaperone-mediated autophagy, a lysosomal import pathway that depends on the 73-kDa heat shock cognate protein and allows the degradation of proteins containing a specific lysosomal import consensus sequence (KFERQ motif), Epidermal growth factor (EGF) or ammonia, but not transforming growth factor beta1, suppresses total protein breakdown in cultured NRK-52E renal epithelial cells, EGF or ammonia prolonged the half-life of glyceraldehyde-3-phosphate dehydrogenase, a classic substrate for chaperone-mediated autophagy, by more than 90%, whereas transforming growth factor pi did not. EGF caused a similar increase in the half-life of the KFERQ-containing paired box-related transcription factor, Pax2. The increase in half-life was accompanied by an increased accumulation of proteins with a KFERQ motif including glyceraldehyde-3-phosphate dehydrogenase and Pax2. Ammonia also increased the level of the Pax2 protein. Lysosomal import of KFERQ proteins depends on the abundance of the 96-kDa lysosomal glycoprotein protein (lgp96), and we found that EGF caused a significant decrease in lgp96 in cellular homogenates and associated with lysosomes, We conclude that EGF in cultured renal cells regulates the breakdown of proteins targeted for destruction by chaperone-mediated autophagy, Because suppression of this pathway results in an increase in Pax2, these results suggest a novel mechanism for the regulation of cell growth.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available