Table 2.
Phosphorylation regulation of autophagy-related kinases.
Kinase | Substrate | Site | Function | Ref. |
---|---|---|---|---|
PI3K | PIP2 | – | Forms second messenger PIP3 | 15 |
PDK1 | AKT | Thr308 | Activates AKT signaling | 22 |
AKT | TSC2 | Ser939/Thr1462 | Dissociates TSC1/2 from lysosome and activates Rheb | 23 |
AMPK | TSC2 | Thr1227/Ser1345 | Regulates cell size and cell survival under energy starvation condition | 24 |
Raptor | Ser722/Ser792 | Mediates a metabolic checkpoint | 25 | |
ULK1 | Ser317/Ser555/Ser777 | Induces autophagy under glucose starvation | 26, 27 | |
PRAS40 | Thr246 | Regulates the activity of mTORC1 | 28 | |
FOXO3a | Ser413/Ser588 | Transcriptionally represses SKP2 | 29 | |
LKB1 | AMPKα | Thr172 | Mediates the prolonged and adaptive activation of AMPK following energy stress | 30 |
CaMKKβ | AMPKα | Thr172 | Activates AMPK in response to increase in cellular Ca2+ | 31 |
TAK1 | AMPKα1/2 | Thr183/Thr172 | Activates AMPKα1/2 | 32 |
mTORC1 | ULK1 | Ser757 | Disrupts the ULK1–AMPK interaction | 26 |
DAP1 | Ser3/Ser51 | Inhibits autophagy indirectly | 33 | |
AMBRA1 | Ser52 | Inhibits autophagy indirectly | 33, 34 | |
TFEB | Ser142 | Inhibits autophagy indirectly | 33, 34 | |
ULK1 | Beclin-1 | Ser14 | Induces autophagy | 16 |
ATG9 | Ser14 | Promotes ATG9 trafficking in response to starvation | 35 | |
ATG4B | Ser316 | Inhibits ATG4B activity and LC3 processing | 36 | |
AMBRA1 | Ser465/Ser635 | Regulates dissociation of AmpRa1–Vps34–beclin-1 from the dynein complex | 37 | |
Raptor | Ser855/Ser859/Ser792 | Inhibits mTORC1 during starvation | 38 | |
ATG13 | Ser318 | Promotes its release to damaged mitochondria | 39 | |
PKCα | ULK1 | Ser423 | Prevents autolysosome formation | 40 |
DAPK1 | Beclin-1 | Thr119 | Liberates beclin-1 from BCL-2 and BCL-XL | 41 |
DAPK3 | Beclin-1 | Ser90 | Regulates autophagy in skeletal muscle | 42 |
DAPK2 | Raptor | Ser721 | Modulates mTORC1 activity and autophagy level | 43 |
JNK1 | BCL-2 | Thr69/Ser70/Ser87 | Dissociates BCL-2 from beclin1 | 44 |
PIM2 | TSC2 | Ser1798 | Relieves the suppression of TSC2 on mTORC1 | 45 |
BAD | Ser112 | Prevents dissociation of BCL-2 from beclin-1 | 46 | |
GSK-3 | Raptor | Ser859 | Regulates mTORC1 | 47 |
LRRK2 | EndoA | Ser75 | Modulates the membrane curvature | 48 |
PINK1 | Parkin | Ser65 | Leads to the aggregation of parkin from cytoplasm to damaged mitochondria | 49 |
– Not applicable.