Purification, Cloning, and Characterization of Nek8, a Novel NIMA-related Kinase, and Its Candidate Substrate Bicd2

We describe the isolation, cloning, and characterization of human Nek8, a new mammalian NIMA-related kinase, and its candidate substrate Bicd2. Nek8 was isolated as a β-casein kinase activity in rabbit lung and has an N-terminal catalytic domain homologous to the Nek family of protein kinases. Nek8 also contains a central domain with homology to RCC1, a guanine nucleotide exchange factor for the GTPase Ran, and a C-terminal coiled-coil domain. Like Nek2, Nek8 prefers β-casein over other exogenous substrates, has shared biochemical requirements for kinase activity, and is capable of autophosphorylation and oligomerization. Nek8 activity is not cell cycle regulated, but like Nek3, levels are consistently higher in G0-arrested cells. During the purification of Nek8 a second protein co-chromatographed with Nek8 activity. This protein, Bicd2, is a human homolog of the Drosophila protein Bicaudal D, a coiled-coil protein. Bicd2 is phosphorylated by Nek8in vitro, and the endogenous proteins associate in vivo. Bicd2 localizes to cytoskeletal structures, and its subcellular localization is dependent on microtubule morphology. Treatment of cells with nocodazole leads to dramatic reorganization of Bicd2, and correlates with Nek8 phosphorylation. This may be indicative of a role for Nek8 and Bicd2 associated with cell cycle independent microtubule dynamics. We describe the isolation, cloning, and characterization of human Nek8, a new mammalian NIMA-related kinase, and its candidate substrate Bicd2. Nek8 was isolated as a β-casein kinase activity in rabbit lung and has an N-terminal catalytic domain homologous to the Nek family of protein kinases. Nek8 also contains a central domain with homology to RCC1, a guanine nucleotide exchange factor for the GTPase Ran, and a C-terminal coiled-coil domain. Like Nek2, Nek8 prefers β-casein over other exogenous substrates, has shared biochemical requirements for kinase activity, and is capable of autophosphorylation and oligomerization. Nek8 activity is not cell cycle regulated, but like Nek3, levels are consistently higher in G0-arrested cells. During the purification of Nek8 a second protein co-chromatographed with Nek8 activity. This protein, Bicd2, is a human homolog of the Drosophila protein Bicaudal D, a coiled-coil protein. Bicd2 is phosphorylated by Nek8in vitro, and the endogenous proteins associate in vivo. Bicd2 localizes to cytoskeletal structures, and its subcellular localization is dependent on microtubule morphology. Treatment of cells with nocodazole leads to dramatic reorganization of Bicd2, and correlates with Nek8 phosphorylation. This may be indicative of a role for Nek8 and Bicd2 associated with cell cycle independent microtubule dynamics. guanine nucleotide exchange factor interleukin-1 phosphate-buffered saline phorbol 12-myristate 13-acetate extracellular signal-regulated kinase c-Jun N-terminal kinase interleukin-6 fluorescence-activated cell sorter microvascular endothelial cells dithiothreitol phenylmethylsulfonyl fluoride hemagglutinin Among the multiple families of related protein kinases that have been described, the mammalian NIMA related kinases, or Neks, have proven to be elusive in their functional characterization. For the most part, the relatedness of these kinases is restricted to sequence homology within the catalytic domain, as none of the Neks appear to be functionally related to NIMA. The prototype for this family, NIMA (never in mitosis, geneA), was originally identified in Aspergillus nidulans as a serine/threonine kinase critical for cell cycle progression. NIMA is specifically required to initiate the cytological aspects of mitosis. Temperature-sensitive mutants of NIMA or overexpression of dominant negative forms of NIMA cause cells to arrest in G2 with uncondensed DNA and interphase microtubules (1Osmani A.H. McGuire S.L. Osmani S.A. Cell. 1991; 67: 283-291Abstract Full Text PDF PubMed Scopus (186) Google Scholar). In addition, overexpression of NIMA in fungus as well as in mammalian cells results in the early onset of mitotic events, including chromatin condensation and depolymerization of microtubules (2Xu X.S. Pu G. Ye R.T. Fincher R.R. McGuire S.L. Osmani A.H. Osmani S.A. EMBO J. 1995; 14: 986-994Crossref PubMed Scopus (126) Google Scholar, 3O'Connell M.J. Norbury C. Nurse P. EMBO J. 1994; 13: 4926-4937Crossref PubMed Scopus (100) Google Scholar, 4Lu K.P. Hunter T. Prog. Cell Cycle Res. 1995; 1: 187-205Crossref PubMed Scopus (39) Google Scholar). The ability of NIMA to functionally regulate mitosis in higher organisms has suggested the existence of a conserved NIMA-like pathway in eukaryotes. However, only in the filamentous ascomycete, Neurospora crassa, and the fission yeast Schizosaccharomyces pombehave functional homologs been identified (5Xu R.T. Wu G. Pu L. Vierula J. Ye K. O'Donnell X.S. Osmani S.A. J. Biol. Chem. 1995; 270: 18110-18116Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar, 6Krien M.J. Bugg S.J. Palatsides M. Asouline G. Morimyo M. O'Connell M.J. J. Cell Sci. 1998; 111: 967-976Crossref PubMed Google Scholar). In recent years, several mammalian Neks have been identified. These typically contain 40–50% sequence identity, which is confined to the catalytic domain. Nek1, the first mammalian Nek to be described, is highly expressed in meiotic germ cells, and was proposed to play a role in meiotic events (7Letwin K. Mizzen L. Motro B. Ben-David Y. Bernstein A. Pawson T. EMBO J. 1992; 11: 3521-3531Crossref PubMed Scopus Google Scholar). as the that is in its P. Sci. A. PubMed Scopus Google Scholar). the mammalian dependent to most the onset of mitosis S.J. J. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google Scholar). with and overexpression of in cells a of required for P. EMBO J. 1998; PubMed Scopus Google Scholar). a coiled-coil protein, and also with protein P. EMBO J. 1998; PubMed Scopus Google Scholar, J. PubMed Scopus Google Scholar). These that to is the of other mammalian a the cell with in G0-arrested cells. However, overexpression have for a K. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, A. A. G. Motro B. PubMed Scopus Google Scholar). Like Nek1, is also highly expressed in germ cells, but A. A. G. Motro B. PubMed Scopus Google Scholar, K. M. Res. PubMed Scopus Google Scholar). other NIMA-related kinases, and their catalytic within the a of Neks M. A. G. Motro B. PubMed Scopus Google Scholar). and to be capable of and the kinase C. M.J. J. Biol. 11: Full Text Full Text PDF PubMed Scopus Google Scholar). the of Nek8 and its candidate Bicd2. Nek8 contains an N-terminal catalytic domain, a C-terminal coiled-coil domain and a central with homology to guanine nucleotide exchange factor Nek8 is related to Neks, substrate and biochemical required for kinase activity. In addition, and autophosphorylation of Nek8 are for its Bicd2 with Nek8 and is phosphorylated by Nek8 in Bicd2 is a human homolog of the Drosophila coiled-coil protein Bicaudal In with microtubules and to Bicd2 a filamentous that is dependent on microtubule morphology. Nek8 with Bicd2 in cells. to Nek3, and activity of Nek8 only the cell with activity in G0-arrested cells. In cells, Nek8 a indicative of which correlates with a dramatic reorganization of Bicd2 isolated with to in and in and and the was in by this by in and the was and the was to a of Nek8 the was with and to a of Nek8 activity and to a of and the Nek8 was a Nek8 activity in for and to a of Nek8 activity with for and to a Nek8 activity to and to a with the and was for Nek8 activity. was for with and of for Nek8 and to a with Nek8 was to the and with was to for Nek8 activity, and was for in a kinase and as of the Nek8 activity in and of the Nek8 was for with and of and by and Nek8 and Bicd2 and to J. J. 1992; PubMed Scopus Google in for and a with with an over and by a by with The was by an protein During a of of a human cell L. PubMed Scopus Google sequence to of the Nek8 was identified. of a that this identified in several rabbit Nek8 was as a to a second human cell was isolated and an of including an the of the Nek8 a new DNA was and to a human in This identified the of The Nek8 was and human cell and by was on and for Nek8 is identified the rabbit Bicd2 by a human sequence This was to several human was in a human cell and as a to and human The was in a of and that the Bicd2 sequence was was by and of a the for Bicd2 is of Nek8 rabbit lung and cells was β-casein as a was in of and of β-casein for by of by and a of β-casein kinase activity was as the of Nek8 to of β-casein in the β-casein of β-casein in and of was with Nek8 for The was by of on proteins and in of and The was by of to a of and the by on a with an by and an protein of identified on an of in the for Nek8 For Nek8 of Nek8 and substrate in as for by of with and by of Nek8 activity is as that of Nek8 to of the in activity is as of Nek8 of protein. For kinase protein, or and of exogenous substrate was to the and as by of by and cells in and and cells in with and microvascular endothelial cells the in and cells with and to the and expressed proteins by with and The Nek8 was Nek8 The Nek8 rabbit was a of the human Nek8 sequence and The Bicd2 rabbit was a of to the and of human Bicd2 For of to in and on Bicd2 was over the and with by protein and The was as a for of the Bicd2 cells as A. L. C. PubMed Scopus Google Scholar). cells in and in and a with and protein was with an and by and Nek8 in kinase cells and for cell cycle and the cells on in a and for Nek8 and cells. for protein and Nek8 was or an or as a for or with in with and and in and and substrate kinase as and cells on cells in with with in and in with and with cells with by with and on a cells for cells. For cells in for by of and to G0-arrested cells for For of cells, cells and for cells by in with nocodazole for cells and for for G2 cells. Cell cycle by of DNA a as in and Scholar). The of exogenous to in to has been a in the of protein kinases. the of a β-casein activity by β-casein kinase L. J. J. Biol. Chem. Full Text PDF PubMed Google Scholar, J. J. 1994; PubMed Scopus Google Scholar, J. PubMed Scopus Google Scholar). This activity was to be for β-casein and not and was protein kinase or and this protein kinase, for the of an β-casein kinase in the of or with and over multiple as in and for β-casein kinase activity, and and as for that the purification of the activity in with in This was in to the of in which of activity was not of on a the of several with and which of these to a β-casein kinase, was in the of in the of exogenous that the was by autophosphorylation or by a was in of the other or not for the kinases are to activity, that the phosphorylated to the β-casein We also on the as this was the second most on the purification activity that not be to and that activity was on that was to that protein was on and by with for and the to the β-casein kinase activity and for was as the ability of a to activity is as of Nek8 of protein. purification is as the of activity to the activity activity that not be to and that activity was on that was to that protein was on and by in a new with for and the to the β-casein kinase activity and for was as the ability of a to activity is as of Nek8 of protein. purification is as the of activity to the activity sequence of the kinase and the protein, and the by of the the phosphorylated was as a conserved of protein kinases 1991; PubMed Scopus Google Scholar). This and other with of human cell and rabbit and with the human sequence isolated and to an for a protein kinase the protein in the of a human of the protein sequence that this was a coiled-coil protein. of the protein sequence that the N-terminal catalytic domain was most to NIMA-related kinases this protein Among the NIMA-related kinases, the sequence of Nek8 is related to Nek1, Nek3, and over the catalytic domain with on human to the Nek8 of over a related protein kinase with a domain was identified and has the and over the catalytic domain. This may to a Drosophila homolog of The only other protein with a kinase domain and a domain is the protein a catalytic domain and and A. C. K. M. M. Sci. A. PubMed Scopus Google Scholar). Nek8 also contains a C-terminal coiled-coil domain, to Nek1, Nek2, and NIMA. The central of Nek8 is of a with homology to as a for the protein and is required for condensation PubMed Google Scholar). The of is a of L. J. C. M. A. 1998; PubMed Scopus Google Scholar). is of a of of and which a have been in a of including GTPase the for A. K. K. A. A. A. C. K. A. M. B. B. M. T. A. 13: PubMed Scopus Google Scholar). However, the role of is not Y. A. R.T. Sci. A. 1998; PubMed Scopus Google Scholar, J. Sci. A. 1998; PubMed Scopus Google Scholar). appear to activity on have activity but appear to be in A. K. K. A. A. A. C. K. A. M. B. B. M. T. A. 13: PubMed Scopus Google Scholar, M. EMBO J. PubMed Scopus Google Scholar). of proteins that Nek8 the required to a for the are conserved However, identified to be for exchange factor activity by and appear not to be well conserved in Nek8 Y. L. A. T. A. J. Biol. PubMed Scopus Google Scholar). its Nek8 contains a coiled-coil domain, as by are to be in by or of of its coiled-coil that a is required for L. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). the protein to and that this was a human homolog of the Drosophila coiled-coil protein, is a coiled-coil protein of B. PubMed Scopus Google G. Cell. Full Text PDF PubMed Scopus Google Scholar). dominant and that with cytoskeletal and to for and In addition, the of is also for its B. Cell. 1991; 67: Full Text PDF PubMed Scopus Google Scholar). independent human homologs have been K. T. M. A. DNA Res. 1998; PubMed Scopus Google Scholar, M. P. PubMed Scopus Google Scholar). human homologs proteins with a coiled-coil appear to be expressed and to K. T. M. A. DNA Res. 1998; PubMed Scopus Google Scholar, M. P. PubMed Scopus Google Scholar). The has with the by K. T. M. A. DNA Res. 1998; PubMed Scopus Google as contains the including an and a the for in an of The other human is to the protein that with Nek8 to a of this protein Bicd2. Nek8 activity rabbit lung the of a β-casein kinase as well as sequence homology to Neks, the biochemical of NIMA-related kinases have also been to kinase which which on β-casein phosphorylated by Nek8, β-casein of β-casein with in the of that Nek8 phosphorylated and of β-casein In the was a and a In addition, a was the in on this a of and as that the of of the β-casein a to the of β-casein by the phosphorylated and the was that the phosphorylated in the to in the We to of the of the in the as with a of for β-casein not For NIMA β-casein with a of K.P. Osmani S.A. J. Biol. Chem. Full Text PDF PubMed Google Scholar). The that in β-casein conserved suggested that this a for substrate phosphorylation. However, of in which the conserved the or the was on the substrate by Nek8 not In kinase the to as the was other β-casein kinases, including and Nek2, have a for over to their Nek8 also have a S.J. J. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google Scholar). In β-casein or the was as a Nek8 activity was with over In addition, of in an of Nek8 activity not results have been for S.J. J. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google Scholar, PubMed Scopus Google Scholar). Nek8 was to as a was not by and its activity was to of not of protein and for their ability to be phosphorylated in by Nek8 also phosphorylated protein, and but to a β-casein not the biochemical substrate and sequence of Nek8 with other NIMA-related kinases is with its role as a identified of this of kinases. The of Nek8 rabbit lung suggested that activity, as of the β-casein kinase activity with in its of with also results in We on cells and that of the was on This has also been for S.J. J. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google Scholar). For autophosphorylation has been proposed to on a conserved within the of the kinase, and of this the kinase functionally (5Xu R.T. Wu G. Pu L. Vierula J. Ye K. O'Donnell X.S. Osmani S.A. J. Biol. Chem. 1995; 270: 18110-18116Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar). We to Nek8 also its by an of that Nek8 was to the and this to the with the the on the on mutants in which or to of on the on its by Nek8, of the ability of the to be phosphorylated was phosphorylated to the of the on sequence NIMA and mammalian Neks for and which have a contain a this that this is an that for Nek8 autophosphorylation may be within the be to of this within the of Nek8 has on autophosphorylation Nek8 on of the may an autophosphorylation the of Nek8 on is that Nek8 autophosphorylation on the kinase that may on within the in Nek8 autophosphorylation activity in vitro, that of Nek8 with for in the of the or higher This in was as of Nek8 in the of on its This that Nek8 autophosphorylation leads to of has also been and has been to of Nek2, in kinase activity L. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). This the that autophosphorylation and higher may also be in Nek8 kinase activity in vivo. The and purification of Nek8 was originally to a β-casein kinase activity specifically by L. J. J. Biol. Chem. Full Text PDF PubMed Google Scholar, J. J. 1994; PubMed Scopus Google Scholar). Nek8 was on sequence β-casein kinase activity. the Nek8 that was to the β-casein kinase activity identified in rabbit to human Nek8 be by human with or factor for or Nek8 was cells and for in kinase activity the as a that was only a of Nek8, Nek8 activity with cells. and factor on Nek8 activity. of the and protein kinases in to or was as that these cells to these This that Nek8 is a β-casein kinase, its activity is to be by to Nek8 have results not that several proteins in of which the protein, or Nek8, was most This protein was also the only to activity, the that this was the the that of the proteins with by to the activity. have been in Nek8 and overexpression of Nek8 in cells results in its M. A. T. A. and G. is that Nek8 activity is by its with other proteins or by This its localization in cells and its ability to This is with the that a may regulate Nek8 activity by or by localization of Nek8 within the have that in multiple and that is required for localization of B. Cell. 1991; 67: Full Text PDF PubMed Scopus Google Scholar). Bicd2 be phosphorylated by Nek8, and in cells in the of or and by and that as Nek8 was capable of of Bicd2 with Nek8 and Bicd2 proteins that Nek8 Bicd2 in The of Bicd2 with Nek8 rabbit lung suggested that these proteins associate in vivo. expressed and in cells. was and by for the of associated that Bicd2 was associated with Nek8, and was not in a as a We also the of with the an The to Bicd2 was in a the that was In addition, also to of endogenous Nek8 and Bicd2 Nek8 was These the that the of Bicd2 with Nek8 activity rabbit lung a these the of Nek8, with a of human of was identified in but was most in and We also levels of in multiple cell including cells, cells, and not on the has been to be for the to Bicd2 K. T. M. A. DNA Res. 1998; PubMed Scopus Google Scholar). the of Bicd2 was to be K. T. M. A. DNA Res. 1998; PubMed Scopus Google Scholar). We also the of Bicd2 and Nek8 in cells by Bicd2 in cells and is in a filamentous of a cytoskeletal of cells with the this that the filamentous is for Bicd2. to endogenous Nek8 by expressed in cells a that with endogenous Bicd2 be to endogenous Nek8 also with Bicd2, and this is In has been to associate with and of with the microtubule a of Cell Res. PubMed Scopus Google Scholar, Google Scholar). with Bicd2 and the of Bicd2 and microtubules in is but not not of with to microtubules the subcellular of Bicd2 with nocodazole or Bicd2 was but in a This that Bicd2 may associate with the microtubule microtubule is for Bicd2 NIMA and have been to be cell cycle also the and activity of Nek8 the cell cells or cells in cell cycle as the of cell cycle as by of endogenous Nek8 in was by with an that Nek8 only the cell with in and cells. in cells, Nek8 was to as a that of Nek8 was The of Nek8 not appear to In cells that the nocodazole the of Nek8 was and Nek8 was of Bicd2 the cell cycle was was expressed and phosphorylated in in G0-arrested cells The of Nek8 that which was in the with the in and cells for the of associated Bicd2 on Nek8, that the of Bicd2 to Nek8 also Nek8 Bicd2 was to Nek8 in and cells, Nek8 was Nek8 activity the cell Nek8 was for activity the as a substrate in kinase that was in Nek8 activity the cell Nek8 activity was consistently higher in G0-arrested cells. This not with the of Nek8 in was in and cells. the of a phosphorylated of Nek8 in cells on Nek8 activity, that other may be in Nek8 protein and activity levels in G0-arrested cells have been for K. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The in Nek8 and activity the cell cycle that the of Nek8 may be by other In a for an β-casein kinase activity to be by identified a protein kinase catalytic domain sequence homology with NIMA-related kinases, Nek8 contains an N-terminal kinase domain and a C-terminal coiled-coil domain, Nek1, Nek2, and NIMA. Nek8 is in that contains a central domain with homology to RCC1, a chromatin for the GTPase the to be in the of are conserved in Nek8, of the for exchange factor activity appear not to be We have been to of Nek8 with a of including Ran, and and is not Nek8 has exchange factor activity. We the that Nek8 may associate with or exchange on other The purification of Nek8 was by a β-casein kinase activity. in β-casein phosphorylated by the of these to a of the conserved in substrate on their ability to be phosphorylated by In the phosphorylated was to a in a is that Bicd2 also contains a and Nek8 contains and or not of these are phosphorylated by Nek8, or this a has not been of the in the has on this may not that be in the of the The on β-casein which are phosphorylated by other Neks have not been identified. Nek8 also biochemical with and Like and Nek2, Nek8 activity is by over as a (7Letwin K. Mizzen L. Motro B. Ben-David Y. Bernstein A. Pawson T. EMBO J. 1992; 11: 3521-3531Crossref PubMed Scopus Google Scholar, S.J. J. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google Scholar). Nek8 activity is also to is to and as a that have also been for PubMed Scopus Google Scholar). The of Nek8 activity to be by its and by its with Bicd2. on the ability of Nek8 to a its that Nek8 on The is highly conserved the mammalian Neks, and is a autophosphorylation in NIMA (5Xu R.T. Wu G. Pu L. Vierula J. Ye K. O'Donnell X.S. Osmani S.A. J. Biol. Chem. 1995; 270: 18110-18116Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar). these that may as an of within Nek8 be required to these of Nek8 that the of was on autophosphorylation of only a of of within the of most kinases results in their that autophosphorylation of first and of other within the We the that other kinases are also required for Nek8 We also that Nek8 autophosphorylation leads to The of of these is with Nek8 Nek8 are and in the of protein, that these are highly structures, and proteins to However, Nek8 as of Nek8 in the of has on its on is with other that as a and results in autophosphorylation and kinase L. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). of is dependent on a C-terminal coiled-coil domain which contains a Nek8 also contains a C-terminal coiled-coil domain, which may be for its For Nek8 and Nek2, has not been to autophosphorylation leads to or The of Nek8 was on a for an β-casein kinase activity by L. J. J. Biol. Chem. Full Text PDF PubMed Google J. J. 1994; PubMed Scopus Google Scholar). identified Nek8 activity in a that was in not that Nek8 to the activity. Nek8 is a protein, the activity by L. J. J. Biol. Chem. Full Text PDF PubMed Google as a protein. and have been to Nek8 kinase in to of Nek8 in cells has on well as of or or of in P. and C. that the of Nek8 as an activity was and the of Nek8 is to be in The purification of Nek8 rabbit lung that a second protein, Bicd2 co-chromatographed with Nek8 activity. Bicd2 is a human homolog of the Drosophila coiled-coil protein, Nek8 Bicd2 in vitro, and the endogenous proteins associate in the that Bicd2 may be an in substrate for the substrate identified for is related to Bicd2. is a coiled-coil protein that with and is phosphorylated by and is for T. P. K. J. Cell Biol. 1998; PubMed Scopus Google Scholar, T. Y. K. J. Cell Biol. PubMed Scopus (186) Google Scholar). We have that the of Bicd2 is in a filamentous a cytoskeletal and expressed Nek8 with Bicd2. in Drosophila the the and of the microtubule and Google Scholar). to with of also by its in the B. Cell. 1991; 67: Full Text PDF PubMed Scopus Google Scholar). of mutants have also the of in or In the homolog Bicd2 may play a filamentous in cells may associate with cytoskeletal with A. S.A. C. P. EMBO J. PubMed Scopus Google that mammalian Bicd2 with a microtubule The localization of Bicd2 is dependent on microtubule as of cells with that microtubules Bicd2 by nocodazole also of Nek8, as by on be to nocodazole also Bicd2 and the subcellular localization of endogenous Nek8 be these Nek8 and activity the cell like Nek3, Nek8 activity was not the cell levels in G0-arrested cells. We a in Nek8 in cells and this with an of Bicd2 associated to is that the are a of the for cell cycle which to microtubule as also in Bicd2 localization in to These may in Nek8 and Bicd2 in to microtubule in a cell cycle independent microtubule of of or cell L. Cell Biol. 1998; PubMed Scopus Google Scholar). of microtubule in with that is to be and of microtubule Cell Biol. 11: PubMed Scopus Google Scholar). We have identified Nek8 as a NIMA-related kinase and an associated coiled-coil protein, Bicd2. Nek8 of the in other mammalian Neks, including substrate and of kinase activity by autophosphorylation and is to that Nek8 may regulate or be by cytoskeletal dynamics. are required to Nek8 and Bicd2 may in that are by microtubule We P. M. and J. for and for the We also for and J. for of the

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