Description:
Phosphorylation of S473 in the PIF motif of RAC-alpha serine/threonine-protein kinase (AKT1) by Serine/threonine-protein kinase mTOR (MTOR) (as part of mTORC2 complex) induces intramolecular interaction with the PIF-binding pocket, resulting in cis-activation of RAC-alpha serine/threonine-protein kinase (AKT1). Dephosphorylation of the PIF motif by PHLPP1/2 (PHLPP1 for Akt2/3 and PHLPP2 for Akt1/3) results in reduced Akt activity, probably by disrupting the interaction with the Akt PIF pocket and thus cis-activation. Participants:
(1) RAC-alpha serine/threonine-protein kinase (AKT1)
Interaction #1 AKT1 - AKT1( intramolecular) intramolecular Interfaces (1) DOC_AGCK_PIF_1 motif ( 469FPQFSY474) in RAC-alpha serine/threonine-protein kinase (AKT1)(2) Protein kinase domain (150-408) in RAC-alpha serine/threonine-protein kinase (AKT1)Interaction Regulation PTM-dependent Induction (Phosphorylation of S473 on RAC-alpha serine/threonine-protein kinase (AKT1)) of the RAC-alpha serine/threonine-protein kinase (AKT1) DOC_AGCK_PIF_1 motif - RAC-alpha serine/threonine-protein kinase (AKT1) Protein kinase domain interaction Regulatory Enzymes for switchModifying enzymes for residue: S473: Serine/threonine-protein kinase mTOR (MTOR)Inferred Regulatory Enzymes for switchPutative modifying enzymes for residue: S473 : ATM, DNA-dependent protein kinase catalytic subunit (PRKDC), Leucine-rich repeat serine/threonine-protein kinase 2 (LRRK2), MAP kinase-activated protein kinase 2 (MAPKAPK2), 1-phosphatidylinositol 3-phosphate 5-kinase (PIKFYVE), Protein kinase C alpha type (PRKCA), Protein kinase C beta type (PRKCB), Serine/threonine-protein kinase D1 (PRKD1), Serine/threonine-protein kinase TBK1 (TBK1), Serine/threonine-protein kinase mTOR (MTOR), Integrin-linked protein kinase (ILK), 3-phosphoinositide-dependent protein kinase 1 (PDPK1).
(1) Common polymorphism in the phosphatase PHLPP2 results in reduced regulation of Akt and protein kinase C.
Brognard et al. J. Biol. Chem. (2009) | |
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