Description: Phosphorylation of S136 in Bcl2 antagonist of cell death (Bad) by RAC-alpha serine/threonine-protein kinase (Akt1) in response to survival and growth signals such as Interleukin-3 (Il3) induces binding to 14-3-3 protein theta (Ywhaq). Binding of 14-3-3 protein theta (Ywhaq) results in dissociation of Bcl2 antagonist of cell death (Bad) from Bcl-2-like protein 1 (Bcl2l1), and thereby inhibits the pro-apoptotic activity of Bcl2 antagonist of cell death (Bad) by allowing liberated Bcl-2-like protein 1 (Bcl2l1) to exert its anti-apoptotic effect on pro-apoptotic proteins like Apoptosis regulator BAX (Bax). Participants: (1) Bcl2 antagonist of cell death (Bad) (2) 14-3-3 protein theta (Ywhaq) Interaction #1 Bad - YwhaqInterfaces (1) LIG_14-3-3_1 motif ( 133RSRSAP138) in Bcl2 antagonist of cell death (Bad)(2) 14-3-3 protein (3-236) in 14-3-3 protein theta (Ywhaq)Interaction Regulation PTM-dependent Induction (Phosphorylation of S136 on Bcl2 antagonist of cell death (Bad)) of the Bcl2 antagonist of cell death (Bad) LIG_14-3-3_1 motif - 14-3-3 protein theta (Ywhaq) 14-3-3 protein interaction Regulatory Enzymes for switchModifying enzymes for residue: S136: RAC-alpha serine/threonine-protein kinase (Akt1)Inferred Regulatory Enzymes for switchPutative modifying enzymes for residue: S136 : PKB_group, RAC-alpha serine/threonine-protein kinase (AKT1), RAC-alpha serine/threonine-protein kinase (Akt1), Serine/threonine-protein kinase PAK 1 (PAK1), cAMP-dependent protein kinase catalytic subunit alpha (PRKACA), cAMP-dependent protein kinase catalytic subunit alpha (Prkaca), cAMP-dependent protein kinase catalytic subunit alpha (PRKACA), Serine/threonine-protein kinase pim-1 (Pim1), Serine/threonine-protein kinase pim-1 (PIM1), Serine/threonine-protein kinase pim-2 (PIM2), Serine/threonine-protein kinase pim-3 (Pim3), Serine/threonine-protein kinase pim-3 (PIM3), Ribosomal protein S6 kinase alpha-1 (RPS6KA1).
(1) Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L) Zha et al. Cell (1996)
(2) Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Datta et al. Cell (1997)
(3) How BAD phosphorylation is good for survival. et al. Nat. Cell Biol. (1999)
(4) 14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation. Datta et al. Mol. Cell (2000) | |
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