Regulation of various proteolytic pathways by insulin and amino acids in human fibroblasts.
Intracellular protein degradation is a regulated process with several proteolytic pathways. Although regulation of macroautophagy has been investigated in some detail in hepatocytes and in few other cells, less is known on this regulation in other cells and proteolytic pathways. We show that in human fibroblasts insulin and amino acids reduce protein degradation by different signalling pathways and that this inhibition proceeds in part via the mammalian target of rapamycin, especially with amino acids, which probably increase lysosomal pH. Moreover, the regulatory amino acids (Phe, Arg, Met, Tyr, Trp and Cys) are partially different from other cells. Finally, and in addition to macroautophagy, insulin and amino acids modify, to different extents and sometimes in opposite directions, the activities of other proteolytic pathways.
Esteban
Inmaculada
I
Laboratorio de Biología Celular, Centro de Investigación Príncipe Felipe, Avda. Autopista del Saler 16, 46013-Valencia, Spain.
Aguado
Carmen
C
Sánchez
Maribel
M
Knecht
Erwin
E
D000596:Amino Acids / Q000494:pharmacology*; D002478:Cells, Cultured; D005347:Fibroblasts; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008854:Microscopy, Electron; D010447:Peptide Hydrolases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases
D000596:Amino Acids; D007328:Insulin; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D010447:Peptide Hydrolases