Reactome | NEK9 phosphorylates NEK6/NEK7

NEK9 phosphorylates NEK6/NEK7

Stable Identifier

R-HSA-2984258

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

Locations in the PathwayBrowser

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Cell Cycle (Homo sapiens)

- Cell Cycle, Mitotic (Homo sapiens)
  - M Phase (Homo sapiens)
    - Mitotic Prophase (Homo sapiens)
      - Nuclear Envelope Breakdown (Homo sapiens)
        
        Activation of NIMA Kinases NEK9, NEK6, NEK7 (Homo sapiens)
        
        NEK9 phosphorylates NEK6/NEK7 (Homo sapiens)

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NEK9, activated by CDK1- and PLK1-mediated phosphorylation, phosphorylates NEK6 on serine residue S206, and NEK7 on serine residue S195. S206 and S195 are located in the activation loop of NEK6 and NEK7, respectively. NEK6 activation is dependent on S206 phosphorylation, although phosphorylation at threonine T202 may augment NEK6 kinase activity. NEK7 activity also depends on phosphorylation of S195. NEK9 remains tightly associated with NEK6 (as well as NEK7) after phosphorylation, and may direct NEK6/NEK7 to specific target (Belham et al. 2003). In addition, irrespective of phosphorylation, binding of the non-catalytic C-terminus of NEK9 to NEK7 (as well as NEK6), relieves autoinhibitory conformation of NEK7/NEK6. The autoinhibitory conformation of NEK7 depends on the formation of a hydrogen bond between tyrosine Y97 (tyrosine Y108 in NEK6) and leucine L180. This Y97-involving hydrogen bond prevents the formation of a salt bridge between lysine K63 and glutamate E82 of NEK7, which is essential for catalysis. Binding of NEK9 is thought to disrupt the hydrogen bond between Y97 and L180 of NEK7 (Y108 and L191 of NEK6) and allow NEK7/NEK6 to achieve active conformation (Richards et al. 2009).

Literature References

PubMed ID	Title	Journal	Year
19941817	An autoinhibitory tyrosine motif in the cell-cycle-regulated Nek7 kinase is released through binding of Nek9 Richards, MW, O'Regan, L, Mas-Droux, C, Blot, JM, Cheung, J, Hoelder, S, Fry, AM, Bayliss, R	Mol. Cell	2009
12840024	A mitotic cascade of NIMA family kinases. Nercc1/Nek9 activates the Nek6 and Nek7 kinases Belham, C, Roig, J, Caldwell, JA, Aoyama, Y, Kemp, BE, Comb, M, Avruch, J	J. Biol. Chem.	2003