Table 1.
General classification of eukaryotic protein kinases. Attending to the target amino acid, protein kinases are classified as serine/threonine and tyrosine kinases. Regarding the catalytic domain, serine/threonine kinases are grouped into the AGC group (protein kinases A, G, and C), Ca2+/calmodulin kinase (CaMK), Cell Kinase 1 (CK1), GMGC group (after CDK, MAPK, GSK, and CDK-like kinases), STE (sterile) kinases, tyrosine-like kinases, and other protein kinases (OPK). Tyrosine kinases are divided into cytoplasmic or receptor (RTK) tyrosine kinases. Each group is formed by different families and presents general traits [34].
| Serine/Threonine Kinases | |||
|---|---|---|---|
| Group | Families | Principal Members | General Traits |
| AGC group | 14 | PKA, PKG, PKC, SGK, AKT/PKB, PDK1, PKN/PRK, RSK, NDR, MAST, YANK, DMPK, GRK, SGK494 | Activated by cyclic nucleotides (PKA by cAMP and PKG by cGMP), regulated by Ca2+, diacylglycerol, or phosphatidylserine (PKC), among others. The “PIF pocket” serves as kinase regulation site and therapeutic target. |
| Ca2+/calmodulin kinase (CaMK) | 17 | CaMK1, CaMK2, PSK, DAPK, MLCK, CASK, PHK, DCAMKL, MAPKAPK, CAMKL, TSSK, PIM, Trbl, PKD, RAD53, Trio, VACAMKL | Binding of Ca2+/CaM complex results in release of the auto-inhibitory domain from the N-terminal kinase domain. Classified into substrate-specific or multifunctional kinases. Key activators of transcription factors. |
| Cell Kinase 1 (CK1) | 3 | CK1, VRK, TTBK | Regulators of signal transduction pathways related to proliferation, cell differentiation, chromosome segregation, and circadian rhythms. |
| CMGC group | 8 | GSKs, MAPK, CDKs, CTD, DYRK, SRPK, CLK, RCK | Essential modulators of the cell cycle (CDKs), glycogen metabolism (GSKs), diverse signaling cascades involved in proliferation, differentiation, neural plasticity (MAPK), and the spliceosomal complex (CLK), among many others. |
| STE | 3 | Ste7/MAP2K, Ste11/MAP3K, Ste20/MAP4K | Also known as MAP2K, MEK, or MKKs, important activators of MAPK family. |
| Tyrosine kinase-like (TKL) | 7 | IRAK, MLK, RIPK, STKR, RAF, LRRK, LISK | Most diverse group with sequence similarity to tyrosine kinases but lacking specific motifs. |
| Other Protein Kinases (OPK) | 37 | PLK, Aur, CAMKK, TLK, ULK, IKK, NAK, NEK, TTK, MOS, TOPK, PEK, WEE, CDC7, NKF1, CK2, BUB, Bud32, Haspin, IRE, NKF4, NKF2, NKF3, NKF5, NRBP, Wnt, SLOB, SCY1, VPS15, TBCK… | Extremely diverse group of Ser/Thr and dual kinases. |
| Tyrosine Kinases | |||
| Group | Families | Principal Members | General Traits |
| Cytoplasmic tyrosine kinases | 32 | ABL, ACK, CSK, FAK, FES, FRK, JAK, SRC, SYK, TEC… | Critical regulators of the immune system by controlling cell growth, proliferation, differentiation, migration, and apoptosis. |
| Receptor tyrosine kinases (RTKs) | 20 | EGFR/ErbB, IR, PDGFR, VEGFR, FGFR, CCKR, NGFR, HGFR, EphR, AXLR, TIER, RYKR, DDRR, RETR, ROSR, LTKR, RORR, MuSKR, LMRR, other RTKs | They contain a transmembrane domain and a highly conserved intracellular C-terminal region with kinase domains. |