title: Signalling by amino acid nutrients.
abstract: It is clear that mTORC1 (mammalian target of rapamycin complex 1) is regulated by the presence of ambient amino acid nutrients. However, the mechanism by which amino acids regulate mTORC1 is still open to question, despite extensive efforts. Our recent work has revealed that PR61ϵ, a B56 family regulatory subunit of PP2A (protein phosphatase 2A), associates with and regulates the activity of MAP4K3 (mitogen-activated protein kinase kinase kinase kinase 3), a protein kinase regulated by amino acid sufficiency that acts upstream of mTORC1. In searching for a physiological process regulated by amino acids, we have demonstrated recently that arginine plays a role in the activation of LPS (lipopolysaccharide)-induced MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase]/ERK signalling in macrophages. PP2A similarly associates with the upstream regulator of MEK in this signalling pathway, TPL-2 (tumour progression locus-2), in response to arginine availability. Thus PP2A is a negative regulator of both MAP4K3 and TPL-2 in both mTORC1 and MEK/ERK signalling pathways.
authors.affiliation: Department of Oncology, University of Alberta, 11560 University Avenue, Edmonton, Alberta, Canada, T6G IZ2.
authors.forename: Lijun
authors.initials: L
authors.lastname: Yan
authors.forename: Richard F
authors.initials: RF
authors.lastname: Lamb
mesh_terms: D000596:Amino Acids / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D005502:Food; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases
chemical_list: D000596:Amino Acids; D046912:Multiprotein Complexes; D011506:Proteins; D011518:Proto-Oncogene Proteins; C543044:MAP4K3 protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D020930:MAP Kinase Kinase Kinases; C069937:MAP3K8 protein, human; D054648:Protein Phosphatase 2