Disease relevance of Nek1

• Mutations in a NIMA-related kinase gene, Nek1, cause pleiotropic effects including a progressive polycystic kidney disease in mice [1].
• Mice with mutations in Nek1 or Nek8 have cystic kidneys; therefore, our discovery that a member of this phylogenetic group of Nek proteins is localized to the same sites in Chlamydomonas and kidney epithelial cells suggests that Neks play conserved roles in the coordination of cilia and cell cycle progression [2].
• Virus produced using the kat system was shown to be free of detectable replication competent retrovirus by an extended provirus mobilization assay, demonstrating that this system is as safe as currently available stable packaging lines [3].

High impact information on Nek1

• Despite its identification with anti-phosphotyrosine antibodies, Nek1 contains sequence motifs characteristic of protein serine/threonine kinases [4].
• These results suggest that Nek1 is a mammalian relative of the fungal NIMA cell cycle regulator [4].
• A mammalian dual specificity protein kinase, Nek1, is related to the NIMA cell cycle regulator and highly expressed in meiotic germ cells [4].
• 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 [4].
• 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 [4].

Biological context of Nek1

• These results suggest that Nek1 may function as a kinase early in the DNA damage response pathway [5].
• A Trypanosoma brucei gene family encoding protein kinases with catalytic domains structurally related to Nek1 and NIMA [6].
• We previously have described a mouse model for polycystic kidney disease (PKD) caused by either of two mutations, kat or kat(2J), that map to the same locus on chromosome 8 [1].
• The mutations, designated kat and kat2J, affect a chromosomal segment homologous to a region of human chromosome 4q35; the altered gene has not yet been identified [7].

Anatomical context of Nek1

• Finally, Nek1-deficient fibroblasts are much more sensitive to the effects of IR-induced DNA damage than otherwise identical fibroblasts expressing Nek1 [5].
• Similarly to Nek1, mSTK2 is expressed ubiquitously among various organs and is upregulated in the testis [8].
• kat: a high-efficiency retroviral transduction system for primary human T lymphocytes [3].

Associations of Nek1 with chemical compounds

• 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 [4].
• The 279-aa N-terminal catalytic domain has highest homology with Nek1, a bifunctional kinase, and NIMA, a protein serine/threonine kinase [6].

Other interactions of Nek1

• In contrast to Nek1 and Nek2, Nek3 levels were not particularly elevated in either the male or the female germ line [9].

References