Table 1 Functions of mammalian Nek kinases
From: Nek family of kinases in cell cycle, checkpoint control and cancer
ID | Functions | Disease associations | Cancer Mutations |
|---|---|---|---|
Nek1 | -excess catalytic activity leads to loss of primary cilia (IMCD3 cells) [45] -Nek1-/- cells display defective G1/S and G2/M checkpoints and DNA repair after IR [64] | -mutation is causal in Kat, Kat2J mouse models of PKD [37] -mutation identified as causal in 2 families with autosomal-recessive short-rib polydactyly syndrome [42] | tumor samples: ovarian (C191F, K779N) large intestinal (N181N*) lung (E25K) cultured cells: lung (A294P) |
Nek2 | -promotes centrosome splitting at G2/M and chromosome segregation [15, 16, 73, 15, 16, 21] -regulates chromosome segregation [73] -catalytic activity inhibited following IR, preventing centrosome separation [62] | -elevated expression in: colangiocarcinoma tumors [74, 75] - elevated expression in MDA-MB-231 and MCF7 cells; knockdown suppresses proliferation in vitro and tumor burden of xenografts in vivo [75] | tumor samples: breast (R115Q, E278K) stomach (G134D) |
Nek3 | -regulates microtubule deacetylation in neurons [30] -regulates prolactin-mediated cytoskeleton rearrangement and motility of T47D breast cancer cells [84] | Â | tumor samples: ovarian (D413Y) cultured cells: stomach(Y398**) |
Nek4 | - knockdown alters sensitivity of MCF7 cells to microtubule poisons taxol and vincristine [31] | Â | tumor samples: large intestinal (R777K) |
Nek5 | -uncharacterized | Â | tumor samples: mouth (K201**) |
Nek6 | -required for mitotic spindle formation and cytokinesis [26] -promotes centrosome separation [27] -activated downstream of Nek9 [85] | -overexpressed in a variety of human tumors [77] -knockdown inhibits HeLa xenografts [77] -Nek6 expression downregulated following p53-induced senescence [78] | tumor samples: ovarian (Y295C, Y291Y*) cultured cells: kidney (I99S) |
Nek7 | -required for mitotic spindle formation and cytokinesis [26] -promotes centrosome separation [27] -activated downstream of Nek9 [85] | -rare Nek7-/- mice survive to birth and exhibit severe growth retardation [28] | tumor samples: lung (G7**) ovarian (I275M) cultured cells: stomach (M8L, V285I) |
Nek8 | -regulation of primary cilia; regulates localization and expression of ciliary proteins PC-1, PC-2 [40, 43] | -mutation is causal in Jck mouse model of PKD [36] -overexpressed in primary human breast tumors [86] | tumor samples: liver (G605D) ovarian (P703***) stomach (R292Q) cultured cells: pancreatic (A197P) skin (L621F) stomach (L341P) |
Nek9 | -regulation of primary cilia; regulates localization and expression of ciliary proteins PC-1, PC-2 [40, 43] | Â | tumor samples: ovarian (V319***) cultured cells: lung (P870S) stomach (V631I, R786Q) |
Nek10 | - regulates establishment of UV-induced G2/M checkpoint [66] - interacts with Raf-1/MEK1 to promote MEK1 autoactivation following UV irradiation [66] | -GWAS identified Nek10 as a strong breast cancer susceptibility locus [80] - various mutations identified in primary tumours and cancer cells lines [82] | tumor samples: ovarian (V319***) cultured cells: lung (P870S) stomach (V631I, R786Q) |
Nek11 | -required for G2/M arrest following IR [55] -activated by Chk1 phosphorylation -phosphorylates DSG motif of Cdc25A leading to its ubiquitination and degradation [55] | Â | tumor samples: ovarian (A66V, V568I, D875Y, F50L, S852S*), lung (R878M) brain (I783V, S797S*) cultured cells: skin (E379K) |