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Mechanistic Investigation into Signaling Specificity of Akt/mTOR Signaling
Author(s) -
Zhou Xin,
Zhang Jin
Publication year - 2016
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.30.1_supplement.lb517
Subject(s) - protein kinase b , pi3k/akt/mtor pathway , akt1 , akt2 , phosphorylation , microbiology and biotechnology , signal transduction , gene isoform , biology , mtorc2 , proto oncogene proteins c akt , compartmentalization (fire protection) , mtorc1 , biochemistry , gene , enzyme
The Akt/mTOR signaling pathway regulates critical cellular processes including cell growth, metabolism, and survival. To achieve the signaling specificity for diverse cellular functions, spatial compartmentalization has been suggested to be an important mechanism. However, the spatial regulation of Akt/mTOR is not well defined and the underlying mechanisms remain poorly understood. We characterize the subcellular Akt/mTOR activity using the newly developed genetically encoded biosensors and further examine the underlying molecular mechanisms of the subcellular Akt/mTOR regulation. We also examine the isoform‐specific regulation of Akt using Akt1 and Akt2 activation reporters. We found conformational changes occur during the activation of Akt isoforms, which are dependent on the presence of the phosphorylatable threonine 308/309 in the activation loop. Mutants of Akt1 and Akt2 carrying phosphomimetic mutations at this residue behave differently in terms of membrane translocation. Take together, our data unveil the location‐specific Akt/mTOR signaling and suggest a model for isoform‐specific activation of Akt. Support or Funding Information NIH grants R01 DK073368 and DP1 CA174423