PMID:12154088

Citation	Noguchi, K, Fukazawa, H, Murakami, Y and Uehara, Y (2002) Nek11, a new member of the NIMA family of kinases, involved in DNA replication and genotoxic stress responses. J. Biol. Chem. 277:39655-65
Abstract	DNA replication and genotoxic stresses activate various checkpoint-associated protein kinases, and checkpoint dysfunction often leads to cell lethality. Here, we have identified new members of the mammalian NIMA family of kinases, termed Nek11L and Nek11S (NIMA-related kinase 11 Long and Short isoform) as novel DNA replication/damage stresses-responsive kinases. Molecular cloning and biochemical studies showed that the catalytic domain of Nek11 is most similar to Nek4 and Nek3, and substrate specificity of Nek11L is distinguishable from those of NIMA and Nek2. The expression of nek11L mRNA increased through S to G(2)/M phase, and subcellular localization of Nek11 protein altered between interphase and prometaphase, suggesting multiple roles of Nek11. We found an activation of Nek11 kinase activity when cells were treated with various DNA-damaging agents and replication inhibitors, and this activation of Nek11 was suppressed by caffeine in HeLaS3 cells. The transient expression of wild-type Nek11L enhanced the aphidicolin-induced S-phase arrest, whereas the aphidicolin-induced S-phase arrest was reduced in the U2OS cell lines expressing kinase-negative Nek11L (K61R), and these cells were more sensitive to aphidicolin-induced cell lethality. Collectively, these results suggest that Nek11 has a role in the S-phase checkpoint downstream of the caffeine-sensitive pathway.
Links	PubMed Online version:10.1074/jbc.M204599200
Keywords	Amino Acid Sequence; Animals; Base Sequence; Blotting, Western; Caffeine/pharmacology; Catalytic Domain; Cell Cycle; Cell Cycle Proteins; Cell Line; Central Nervous System Stimulants/pharmacology; Cloning, Molecular; DNA/biosynthesis; DNA, Complementary/metabolism; Exons; Expressed Sequence Tags; Flow Cytometry; Green Fluorescent Proteins; HeLa Cells; Humans; Interphase; Introns; Luminescent Proteins/metabolism; Metaphase; Microscopy, Fluorescence; Molecular Sequence Data; Phosphorylation; Phylogeny; Precipitin Tests; Protein Binding; Protein Isoforms; Protein Kinases/chemistry; Protein Kinases/physiology; Protein Structure, Tertiary; Protein-Serine-Threonine Kinases/chemistry; Protein-Serine-Threonine Kinases/physiology; RNA/metabolism; S Phase; Sequence Homology, Amino Acid; Software; Substrate Specificity; Time Factors; Tumor Cells, Cultured
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:NEK11		GO:0016572: histone phosphorylation	ECO:0000315:		P		Figure 2B.	complete CACAO 6103
HUMAN:NEK11		GO:1901990: regulation of mitotic cell cycle phase transition	ECO:0000315:		P		Figure 6.	complete CACAO 6105
HUMAN:NEK11	involved_in	GO:0016572: histone phosphorylation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:NEK11	involved_in	GO:1901990: regulation of mitotic cell cycle phase transition	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:NEK11	involved_in	GO:0044772: mitotic cell cycle phase transition	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

See Help:References for how to manage references in GONUTS.