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The mTOR pathway senses the glucose sufficiency through an interaction between Rheb and Glyceraldehyde‐3‐phosphate dehydrogenase
Author(s) -
Lee Mi nam
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a99-b
Subject(s) - rheb , glyceraldehyde 3 phosphate dehydrogenase , dehydrogenase , chemistry , pi3k/akt/mtor pathway , glyceraldehyde , biochemistry , microbiology and biotechnology , biology , enzyme , signal transduction , mtorc1
Rheb (Ras homology enriched in brain) is a member of the Ras family, which acts as a positive regulator of mTOR signaling which controls the cell growth and cell cycle progression. We identify the glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) as a binding partner of Rheb. GAPDH binds to Rheb directly and is co‐immunoprecipitated with Rheb in cells overexpressing Rheb and GAPDH. Binding of Rheb to GAPDH is independent of Rheb nucleotide charging both in vivo and in vitro . We show that GAPDH substrate, glyceraldehyde‐3‐phosphate (G3P) inhibits the GAPDH‐Rheb binding more effectively than the other factors do. The inhibition of glycolytic flux via glucose starvation or treatment of 2‐deoxyglucose enhances the interaction between Rheb and GAPDH. We also find that glucose starvation inhibits the binding of Rheb to mTOR. Moreover, we show that GAPDH inhibits the mTOR kinase activity, which can be overcome by addition of G3P in mTOR kinase assay. In this study, we suggest there is the novel mechanism that the mTOR pathway integrates glucose sufficiency through direct interaction between glycolytic enzyme GAPDH and Rheb. GAPDH reflects the degree of glucose sufficiency through being charged with G3P, so the uncharged GAPDH (the form of GAPDH under glucose starvation condition) can bind to Rheb and lead to dissociation of Rheb from the mTOR complex.

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