Lanthionine synthetase C-like protein 2 (LanCL2) is a novel regulator of Akt.

The serine/threonine protein kinase Akt controls a wide range of biochemical and cellular processes under the modulation of a variety of regulators. In this study, we identify the lanthionine synthetase C-like 2 (LanCL2) protein as a positive regulator of Akt activation in human liver cells. LanCL2 knockdown dampens serum- and ...
insulin-stimulated Akt phosphorylation, whereas LanCL2 overexpression enhances these processes. Neither insulin receptor phosphorylation nor the interaction between insulin receptor substrate and phosphatidylinositide 3-kinase (PI3K) is affected by LanCL2 knockdown. LanCL2 also does not function through PP2A, a phosphatase of Akt. Instead, LanCL2 directly interacts with Akt, with a preference for inactive Akt. Moreover, we show that LanCL2 also binds to the Akt kinase mTORC2, but not phosphoinositide-dependent kinase 1. Whereas LanCL2 is not required for the Akt-mTORC2 interaction, recombinant LanCL2 enhances Akt phosphorylation by target of rapamycin complex 2 (mTORC2) in vitro. Finally, consistent with a function of Akt in regulating cell survival, LanCL2 knockdown increases the rate of apoptosis, which is reversed by the expression of a constitutively active Akt. Taken together, our findings reveal LanCL2 as a novel regulator of Akt and suggest that LanCL2 facilitates optimal phosphorylation of Akt by mTORC2 via direct physical interactions with both the kinase and the substrate.
Mesh Terms:
Alanine, Apoptosis, Blotting, Western, Cell Line, Transformed, Cell Survival, HEK293 Cells, Hep G2 Cells, Humans, Mechanistic Target of Rapamycin Complex 2, Membrane Proteins, Microscopy, Fluorescence, Multiprotein Complexes, Nuclear Proteins, Phosphorylation, Protein Binding, Proto-Oncogene Proteins c-akt, RNA Interference, Sulfides, TOR Serine-Threonine Kinases
Mol. Biol. Cell
Date: Dec. 01, 2014
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