RRC ID 51371
著者 Narbonne P, Maddox PS, Labbé JC.
タイトル DAF-18/PTEN signals through AAK-1/AMPK to inhibit MPK-1/MAPK in feedback control of germline stem cell proliferation.
ジャーナル PLoS Genet
Abstract Under replete growth conditions, abundant nutrient uptake leads to the systemic activation of insulin/IGF-1 signalling (IIS) and the promotion of stem cell growth/proliferation. Activated IIS can stimulate the ERK/MAPK pathway, the activation of which also supports optimal stem cell proliferation in various systems. Stem cell proliferation rates can further be locally refined to meet the resident tissue's need for differentiated progeny. We have recently shown that the accumulation of mature oocytes in the C. elegans germ line, through DAF-18/PTEN, inhibits adult germline stem cell (GSC) proliferation, despite high systemic IIS activation. We show here that this feedback occurs through a novel cryptic signalling pathway that requires PAR-4/LKB1, AAK-1/AMPK and PAR-5/14-3-3 to inhibit the activity of MPK-1/MAPK, antagonize IIS, and inhibit both GSC proliferation and the production of additional oocytes. Interestingly, our results imply that DAF-18/PTEN, through PAR-4/LKB1, can activate AAK-1/AMPK in the absence of apparent energy stress. As all components are conserved, similar signalling cascades may regulate stem cell activities in other organisms and be widely implicated in cancer.
巻・号 13(4)
ページ e1006738
公開日 2017-4-1
DOI 10.1371/journal.pgen.1006738
PII PGENETICS-D-16-01937
PMID 28410423
PMC PMC5409174
MeSH AMP-Activated Protein Kinases / genetics Aging / genetics Animals Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Cell Differentiation / genetics* Cell Proliferation / genetics Germ Cells Insulin / metabolism Insulin-Like Growth Factor I / genetics Longevity / genetics* Mitogen-Activated Protein Kinase 1 / genetics* Mitogen-Activated Protein Kinase 1 / metabolism Oocytes / metabolism PTEN Phosphohydrolase / genetics Protein Serine-Threonine Kinases / genetics* Protein Serine-Threonine Kinases / metabolism Signal Transduction / genetics Stem Cells / metabolism
IF 5.175
引用数 8
リソース情報
線虫 tm1944