Function
- Serine/threonine protein kinase 1 (Chk1) phosphorylates cdc25A, cdc25B and cdc25C. Upon phosphorylation, cdc25 binds adaptor protein and the cell is prevented from entering mitosis[1].
- Cyclin-dependent kinases
- Chk2 (Checkpoint kinase 2) phosphorylates cdc25C at Ser-216.
- Chk6 called also Aurora A is critical for the formation of mitotic spindles during cellular mitosis. Chk6 is phosphorylated at residues Thr287 and Thr288[2].
- Chk13 (Polo-like kinase 1 or Plk1) functions during the M phase of the cell cycle including the regulation of centrosome maturation and spindle assembly. Chk13 binds and phosphorylates proteins which are already phosphorylated on a motif recognized by its POLO-box domain (Pbd) at the C terminal. Human Chk13 contains catalytic domain (residues 13-345) and POLO-box domain (residues 345-603)[3].
- Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase. GSK-3 is active in a number of intracellular signaling pathways. GSK-3 regulates glycogen synthase as well as other proteins. GSK-3 inhibition is studied as a therapeutic target in diseases like Alzheimer, diabetes, bipolar disorder and some cancers[5].
- B-Raf is related to retroviral oncogenes and participates in cellular signal transduction. B-Raf domains include the kinase domain - residues 444-721 and Ras-binding domain - residues 153-237. Mutated B-Raf was found in some human cancers[6].
See more in B-RAF with PLX4032; Mitogen-activated protein kinase cascade.
- Gcn2 (Generl Control Nonderepressible 2) senses amino acid deficiency by binding to uncharged tRNA[9].
- Protein kinase B (PKB), also known as AKT, is the collective name of a set of three serine/threonine-specific protein kinases that play key roles in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration. For example of AKT1 see 3mv5. Rac-α or AKT1 acts in cell growth and survival. Rac-β or AKT2 acts in metabolism. Rac-γ or AKT3 acts in the nervous system.
For details on Snf1-related kinase see
Structure of Anticancer Ruthenium Half-Sandwich Complex Bound to Glycogen Synthase Kinase 3ß [10]
A crystal structure of an bound to the protein kinase glycogen synthase kinase 3ß (GSK-3ß) has been determined and reveals that the inhibitor binds to the via an induced fit mechanism utlizing several and . Importantly, the metal is not involved in any direct interaction with the protein kinase but fulfills a purely structural role. The unique, bulky molecular structure of the half-sandwich complex with the CO-ligand oriented perpendicular to the pyridocarbazole heterocycle allows the complex to stretch the whole distance and to interact tightly with . Although this complex is a conventional ATP-competitive binder, the unique shape of the complex allows novel interactions with the glycine-rich loop which are crucial for binding potency and selectivity. It can be hypothesized that coordination spheres which present other ligands towards the glycine-rich loop might display completely different protein kinase selectivities.
3D structures of serine/threonine protein kinase
Serine/threonine protein kinase 3D structures
