TABLE 2.
Phosphorylation events regulating cellular apoptosis. BAD, BCL-2 associated agonist of cell death; BAX, BCL-2-associated X protein; BID, BH3 interacting-domain death agonist; BIM, BCL-2 interacting mediator of cell death; BCL-2, B cell lymphoma 2; CDK5, cyclin-dependent kinase 5; CKI, casein kinase I; CKII, casein kinase II; ERK, extracellular signal-regulated kinase; GSK3β, glycogen synthase kinase-3 beta; HER2, human epidermal growth factor receptor 2; JNK, Jun N-terminal kinase; MEK, mitogen-activated protein kinase kinase; MCL-1, myeloid cell leukaemia sequence 1; NOXA, phorbol-12-myristate-13-acetate-induced protein 1; PAK1, P21 (RAC1) Activated Kinase 1; PKCα, protein kinase C alpha; PUMA, p53 upregulated modulator of apoptosis.
| Target | Phospho site | Kinase | Associated outcome |
|---|---|---|---|
| BAD | S112, S136 | AKT | Suppression of apoptosis induction |
| BAD | S112 + S136 + S155 | AKT | BAD degradation |
| BAD | S111 | PAK1 | Promotes cell survival |
| BID | S61, S64 | CKI, CKII | Suppression of apoptosis induction |
| BID | T59 | JNK | Apoptosis induction despite suppressed caspase-8 cleavage |
| BID | S61 | ATM | Maintenance of the IR-induced cell cycle checkpoint |
| BID | S66 (increased phosphorylation) | Undefined | Induction of apoptosis following mitotic arrest |
| BIM | S109, T110 | MEK | Neuron protection against BIM-induced cell death |
| BIM | S65, S69 | ERK1/2 | Suppression of apoptosis |
| BIM | S44, T56, S58 | JNK | Activation of BIM to induce apoptosis |
| BIM | S65 | JNK | Activation of mitochondrial driven mitosis in neurons |
| BIM | S87 | AKT | Induction of ubiquitination to promote cell survival |
| BIM | S93, S94, S98 | Aurora A | BIM degradation to promote successful completion of the cell cycle |
| NOXA | S13 | CDK5 | Suppression of apoptosis upon glucose availability |
| PUMA | Y152, Y172 | HER2 | PUMA degradation and suppression of apoptosis induction |
| BAX | S163 | GSK3β | Reduction of BAX mitochondrial localisation and pore formation |
| BAX | Y108 | BMX | Maintenance of BAX in an inactive conformation to prevent apoptosis |
| BCL-2 | T56, S70, T74, S87 | JNK | Induction of mitogenic signalling to promote apoptosis? |
| BCL-2 | S70 | PKCα | Increased resistance to apoptosis |
| MCL-1 | T92, T163 | ERK | Prevention of MCL-1 degradation to promote cell survival |
| MCL-1 | S121, T163 (high H2O2 conditions) | JNK | Induction of ROS-driven apoptosis |