Critical role for PI3-kinase in regulating the use of proteins as an amino acid source Journal Article

   

Authors:	Palm, W.; Araki, J.; King, B.; DeMatteo, R. G.; Thompson, C. B.
Article Title:	Critical role for PI3-kinase in regulating the use of proteins as an amino acid source
Abstract:	Ras-transformed cells can grow in amino acid-poor environments by recovering amino acids through macropinocytosis and lysosomal catabolism of extracellular proteins. However, when studying nontransformed fibroblasts, we found that Ras GTPases are dispensable for growth-factor–stimulated macropinocytosis and lysosomal catabolism of extracellular proteins. Instead, we establish a critical role for phosphatidylinositol 3-kinase (PI3-kinase) signaling in cell proliferation that is supported by protein macropinocytosis. Downstream of PI3-kinase, distinct effectors have opposing roles in regulating uptake and catabolism of extracellular proteins. Rac1 and PLC are required for nutritional use of extracellular proteins. In contrast, Akt suppresses lysosomal catabolism of ingested proteins when free amino acids are abundant. The interplay between these pathways allows cells with oncogenic PIK3CA mutations or PTEN deletion to grow using diverse amino acid sources. Thus, the prevalence of PI3-kinase and PTEN mutations in cancer may result in part because they allow cells to cope with fluctuating nutrient availability. © 2017, National Academy of Sciences. All rights reserved.
Keywords:	macropinocytosis; cancer metabolism; cellular nutrient acquisition; lysosomal protein catabolism; pi3-kinase signaling pathway
Journal Title:	Proceedings of the National Academy of Sciences of the United States of America
Volume:	114
Issue:	41
ISSN:	0027-8424
Publisher:	National Academy of Sciences
Date Published:	2017-10-10
Start Page:	E8628
End Page:	E8636
Language:	English
DOI:	10.1073/pnas.1712726114
PROVIDER:	scopus
PMCID:	PMC5642723
PUBMED:	28973876
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85030748931&doi=10.1073%2fpnas.1712726114&partnerID=40&md5=56cea205130f8e387d6d440440f5b4ea
Notes:	Article -- Export Date: 2 November 2017 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/116655