Serine/threonine protein kinase

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].

• Chk11 see STK11.

• Chk Pak see Student Project 1 for UMass Chemistry 423 Spring 2015^[4].

• 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.

• c-Raf is part of the MAPK pathway. c-Raf domains include the kinase domain - residues 323-618, cysteine-rich domain – residues 136-187 and Ras-binding domain - residues 51-132. Mutations of c-Raf are possible causes of Noonan syndrome^[7]. For details on c-Raf see Molecular Playground/C-Raf and Mitogen-activated protein kinase cascade..

• mTOR (mammalian target of Rapamycin) integrates the input from insulin, growth factors and amino acids. Rapamycin inhibits mTOR by association with FKBP12^[8]. See also PI3K/AKT/mTOR signaling pathway.

• Gcn2 (Generl Control Nonderepressible 2) senses amino acid deficiency by binding to uncharged tRNA^[9].

• PRK1 or serine/threonine protein kinase N1 belongs th protein kinase C family. PRK1 may mediate the Rho-independent signaling pathway. For more details see Student Project 1 for UMass Chemistry 423 Spring 2015.

• Pim see Proto-oncogene serine/threonine-protein kinase

• Leucine-rich repeat serine/threonine-protein kinase 2 (LRRK2)

• 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

• ABA-regulated SNRK2 Protein Kinase
  
• ABA Signaling Pathway.

• See also Receptor protein serine/threonine kinases

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