30 Aug [MCE] Protein kinases—important regulator of cell signaling
Protein phosphorylation is one of the most common and important post-translational modifications, and it regulates a variety of cellular signaling pathways. Protein kinases regulate protein phosphorylation by catalyzing the transfer of the terminal phosphate group (PO4) of ATP to the hydroxyl group of an amino acid residue[1]. In eukaryotes, protein kinases phosphorylate mainly Ser or Thr residue (protein Ser/Thr kinases, PSKs) or Tyr residue (protein Tyr kinases, PTKs)[2]. There are many subfamilies of protein kinases, as shown in Table 1.
| Famliy | Members |
| Protein Ser/Thr kinases | |
| AGC famliy | PKA, PKC, PKG |
| CaMK | CaMK I, CaMK II, CaMK III, CaMK IV, CaMK V |
| Casein kinase | CK1, CK2 |
| CMGC famliy | CDK, MAPK (ERK, JNK, p38), GSK3, CLK |
| STE famliy | STE7 (MEK), STE11, STE20 (MAP4K) |
| TKL famliy | IRAK, LRRK, LIMK, MLK, RIPK, RSTK (TGFBR, BMPR) |
| Protein Tyr kinases | |
| Non-receptor famliy | ABL, ACK, FAK, JAK, SRC, SYK |
| Receptor famliy | ALK, EGFR, FGFR, MET, PDGFR, RET, ROR, ROS, TIE, TRK, VEGFR |
Table 1. Subfamilies and members of protein kinases
Take the serine-threonine kinase AKT (also known as protein kinase B or PKB) as an example. AKT is activated downstream of PI3K activation, which is mediated by receptor tyrosine kinase (RTK), cytokine receptors, integrins, or G protein-coupled receptors (GPCRs)[3]. PI3K phosphorylates PIP2 to produce PIP3, which recruits AKT to the plasma membrane. Then AKT is phosphorylated by PDK1 and rapamycin (mTOR) complex 2 (mTORC2). Activated AKT further activates a few key downstream effectors, including mTOR complex 1 (mTORC1), GSK3, and members of the forkhead box O (FOXO) family[4]. The PI3K/AKT/mTOR signaling network plays a major role in promoting cell survival, growth, and proliferation, by inducing various changes to cellular metabolism.
Figure. 1 The overview of PI3K/AKT/mTOR signaling pathway[4]
MedChemExpress, your partner for bioactive compounds
• 60,000+ Bioactive inhibitors & Agonists targeting 20+ classic signaling pathways
• 6,000+ Research institutions and drug discovery companies customers
• 10,000+ Recombinant proteins with superior biological activity
• 200+ Bioactive compound libraries
References:
[1] Bioorg Chem. 2011;39 (5-6):192-210.
[2] Int J Mol Med. 2017;40(2):271-280.
[3] Nat Rev Cancer. 2020;20(2):74-88.
[4] Mol Cancer. 2019;18(1):26.
Request Your Quote