title: A mammalian dual specificity protein kinase, Nek1, is related to the NIMA cell cycle regulator and highly expressed in meiotic germ cells.
abstract: Screening of mouse cDNA expression libraries with antibodies to phosphotyrosine resulted in repeated isolation of cDNAs that encode a novel mammalian protein kinase of 774 amino acids, termed Nek1. Nek1 contains an N-terminal protein kinase domain which is most similar (42% identity) to the catalytic domain of NIMA, a protein kinase which controls initiation of mitosis in Aspergillus nidulans. In addition, both Nek1 and NIMA have a long, basic C-terminal extension, and are therefore similar in overall structure. Despite its identification with anti-phosphotyrosine antibodies, Nek1 contains sequence motifs characteristic of protein serine/threonine kinases. The Nek1 kinase domain, when expressed in bacteria, phosphorylated exogenous substrates primarily on serine/threonine, but also on tyrosine, indicating that Nek1 is a dual specificity kinase with the capacity to phosphorylate all three hydroxyamino acids. Like NIMA, Nek1 preferentially phosphorylated beta-casein in vitro. In situ RNA analysis of nek1 expression in mouse gonads revealed a high level of expression in both male and female germ cells, with a distribution consistent with a role in meiosis. These results suggest that Nek1 is a mammalian relative of the fungal NIMA cell cycle regulator.
authors.affiliation: Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Letwin
authors.forename: L
authors.initials: L
authors.lastname: Mizzen
authors.forename: B
authors.initials: B
authors.lastname: Motro
authors.forename: Y
authors.initials: Y
authors.lastname: Ben-David
authors.forename: A
authors.initials: A
authors.lastname: Bernstein
authors.forename: T
authors.initials: T
authors.lastname: Pawson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001233:Aspergillus nidulans / Q000166:cytology / Q000201:enzymology / Q000235:genetics; D001483:Base Sequence; D015152:Blotting, Northern; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004822:Epididymis / Q000201:enzymology; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D015870:Gene Expression; D015723:Gene Library; D005822:Genetic Vectors; D008168:Lung / Q000201:enzymology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D000072380:NIMA-Related Kinase 1; D010053:Ovary / Q000201:enzymology; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013737:Testis / Q000201:enzymology; D013950:Thymus Gland; D014158:Transcription, Genetic
chemical_list: D018797:Cell Cycle Proteins; D011993:Recombinant Fusion Proteins; D012313:RNA; D004247:DNA; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D000072380:NIMA-Related Kinase 1; C000606920:Nek1 protein, mouse; D017346:Protein Serine-Threonine Kinases