Phosphatidylinositol 3-kinase activity is required for epidermal growth factor to suppress proteolysis.

Journal of the American Society of Nephrology : JASN
Harold A FranchJie Du

Abstract

Suppression of protein breakdown occurs commonly in cell growth, but the pathways responsible for controlling proteolysis are poorly understood. Protein breakdown in NRK-52E renal epithelial cells treated with epidermal growth factor (EGF) and intracellular signaling inhibitors or dominant negative signaling molecules contained in an adenoviral vector were measured. The tyrosine kinase inhibitor, herbimycin A, eliminated the suppression of proteolysis induced by EGF. In contrast, the Src inhibitor, PP1, had no effect. Expression of dominant negative H-RasY57 blocked the ability of EGF to stimulate downstream targets of Ras and also reduced the ability of EGF to suppress proteolysis. Inhibiting MEK did not influence the ability of EGF to suppress proteolysis, but the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor, LY249002, stimulated basal proteolysis and completely eliminated the proteolytic response to EGF. Use of an adenovirus that expresses a dominant negative p85 subunit of class 1 PI 3-kinase completely blocked the ability of EGF to suppress proteolysis, whereas use of an adenovirus expressing a K227E constitutively active p110 subunit reproduced the reduction in protein breakdown. It was concluded that EGF suppres...Continue Reading

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Citations

Jul 10, 2002·Current Opinion in Nephrology and Hypertension·Harold A Franch
Jun 14, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Won KimSung Kwang Park
Aug 25, 2004·The International Journal of Biochemistry & Cell Biology·Ashish MasseyAna Maria Cuervo
Apr 6, 2005·Current Opinion in Clinical Nutrition and Metabolic Care·Harold A Franch, S Russ Price
Jan 18, 2006·The Journal of Physiology·Georges DaoudJulie Lafond
Aug 4, 2006·Journal of the American Society of Nephrology : JASN·Wen ShenHarold A Franch
Apr 28, 2007·Journal of Renal Nutrition : the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation·Harold A Franch
Jan 1, 2004·The Journal of Clinical Investigation·Jie DuWilliam E Mitch
Oct 21, 2010·Biochimica Et Biophysica Acta·Nadezhda N ZheleznovaAlexander Staruschenko
Apr 26, 2011·Toxicology Letters·Sunhapas SoodvilaiVaranuj Chatsudthipong

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