NEK6/NEK7 phosphorylates NUP98

Stable Identifier
R-HSA-2990880
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Phosphorylation of NUP98 by NEK6 (and/or NEK7) promotes nuclear envelope permeabilization by initiating nuclear pore complex (NPC) disassembly. Two NUP98 serine residues, S591 and S822 (referring to NUP98 splice variant NUP98-4; these residues correspond to S608 and S839 of NUP98 splice variant NUP98-3), are phosphorylated on NUP98 isolated from mitotic HeLa cells (human cervical cancer cell line). These serine residues match the NEK6 target site consensus and are phosphorylated by NEK6 in vitro. Both sites can also be phosphorylated in vitro by NEK7 and weakly by NEK2. As NEK7 but not NEK2 was shown to be involved, with NEK6, in nuclear envelope permeabilization, NEK2 is not shown as the NUP98 kinase. Phosphorylated NUP98 dissociates from the NPC (Laurell et al. 2011). As NUP98 localizes to both sides of the NPC, cytosolic and nucleoplasmic (Griffis et al. 2003), the reaction shows a portion of NUP98 being released to the cytosol, and a portion of NUP98 dissociating into the nucleus, similar to what is observed by immunocytochemistry (Laurell et al. 2011).

Literature References
PubMed ID Title Journal Year
12589057 Nup98 localizes to both nuclear and cytoplasmic sides of the nuclear pore and binds to two distinct nucleoporin subcomplexes

Griffis, ER, Xu, S, Powers, MA

Mol. Biol. Cell 2003
21335236 Phosphorylation of Nup98 by multiple kinases is crucial for NPC disassembly during mitotic entry

Laurell, E, Beck, K, Krupina, K, Theerthagiri, G, Bodenmiller, B, Horvath, P, Aebersold, R, Antonin, W, Kutay, U

Cell 2011
Participants
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Catalyst Activity
Catalyst Activity
Title
protein serine/threonine kinase activity of p-3S,2T-NEK9: p-S206-NEK6/ p-S195-NEK7 [cytosol]
Physical Entity
Activity
Orthologous Events
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