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].
  
• 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].

• 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 ATK1 see 3mv5.

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