• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of embojLink to Publisher's site
EMBO J. Oct 1992; 11(10): 3521–3531.
PMCID: PMC556810

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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (3.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Amon A, Surana U, Muroff I, Nasmyth K. Regulation of p34CDC28 tyrosine phosphorylation is not required for entry into mitosis in S. cerevisiae. Nature. 1992 Jan 23;355(6358):368–371. [PubMed]
  • Bachvarova R. Gene expression during oogenesis and oocyte development in mammals. Dev Biol (N Y 1985) 1985;1:453–524. [PubMed]
  • Ben-David Y, Letwin K, Tannock L, Bernstein A, Pawson T. A mammalian protein kinase with potential for serine/threonine and tyrosine phosphorylation is related to cell cycle regulators. EMBO J. 1991 Feb;10(2):317–325. [PMC free article] [PubMed]
  • Cortay JC, Nègre D, Cozzone AJ. Analyzing protein phosphorylation in prokaryotes. Methods Enzymol. 1991;200:214–227. [PubMed]
  • Crews CM, Alessandrini AA, Erikson RL. Mouse Erk-1 gene product is a serine/threonine protein kinase that has the potential to phosphorylate tyrosine. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8845–8849. [PMC free article] [PubMed]
  • Dailey D, Schieven GL, Lim MY, Marquardt H, Gilmore T, Thorner J, Martin GS. Novel yeast protein kinase (YPK1 gene product) is a 40-kilodalton phosphotyrosyl protein associated with protein-tyrosine kinase activity. Mol Cell Biol. 1990 Dec;10(12):6244–6256. [PMC free article] [PubMed]
  • Dingwall C, Laskey RA. Nuclear targeting sequences--a consensus? Trends Biochem Sci. 1991 Dec;16(12):478–481. [PubMed]
  • Dolci S, Williams DE, Ernst MK, Resnick JL, Brannan CI, Lock LF, Lyman SD, Boswell HS, Donovan PJ. Requirement for mast cell growth factor for primordial germ cell survival in culture. Nature. 1991 Aug 29;352(6338):809–811. [PubMed]
  • Featherstone C, Russell P. Fission yeast p107wee1 mitotic inhibitor is a tyrosine/serine kinase. Nature. 1991 Feb 28;349(6312):808–811. [PubMed]
  • Godin I, Deed R, Cooke J, Zsebo K, Dexter M, Wylie CC. Effects of the steel gene product on mouse primordial germ cells in culture. Nature. 1991 Aug 29;352(6338):807–809. [PubMed]
  • Goldman DS, Kiessling AA, Millette CF, Cooper GM. Expression of c-mos RNA in germ cells of male and female mice. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4509–4513. [PMC free article] [PubMed]
  • Gould KL, Nurse P. Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis. Nature. 1989 Nov 2;342(6245):39–45. [PubMed]
  • Hanks SK, Quinn AM, Hunter T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science. 1988 Jul 1;241(4861):42–52. [PubMed]
  • Henikoff S. Unidirectional digestion with exonuclease III in DNA sequence analysis. Methods Enzymol. 1987;155:156–165. [PubMed]
  • Howell BW, Afar DE, Lew J, Douville EM, Icely PL, Gray DA, Bell JC. STY, a tyrosine-phosphorylating enzyme with sequence homology to serine/threonine kinases. Mol Cell Biol. 1991 Jan;11(1):568–572. [PMC free article] [PubMed]
  • Jones DG, Rosamond J. Isolation of a novel protein kinase-encoding gene from yeast by oligodeoxyribonucleotide probing. Gene. 1990 May 31;90(1):87–92. [PubMed]
  • Kamps MP, Sefton BM. Identification of multiple novel polypeptide substrates of the v-src, v-yes, v-fps, v-ros, and v-erb-B oncogenic tyrosine protein kinases utilizing antisera against phosphotyrosine. Oncogene. 1988 Apr;2(4):305–315. [PubMed]
  • Keshet E, Rosenberg MP, Mercer JA, Propst F, Vande Woude GF, Jenkins NA, Copeland NG. Developmental regulation of ovarian-specific Mos expression. Oncogene. 1988 Mar;2(3):235–240. [PubMed]
  • Keshet E, Itin A, Fischman K, Nir U. The testis-specific transcript (ferT) of the tyrosine kinase FER is expressed during spermatogenesis in a stage-specific manner. Mol Cell Biol. 1990 Sep;10(9):5021–5025. [PMC free article] [PubMed]
  • Knighton DR, Zheng JH, Ten Eyck LF, Xuong NH, Taylor SS, Sowadski JM. Structure of a peptide inhibitor bound to the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase. Science. 1991 Jul 26;253(5018):414–420. [PubMed]
  • Knighton DR, Zheng JH, Ten Eyck LF, Ashford VA, Xuong NH, Taylor SS, Sowadski JM. Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase. Science. 1991 Jul 26;253(5018):407–414. [PubMed]
  • Lee MG, Nurse P. Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2. Nature. 1987 May 7;327(6117):31–35. [PubMed]
  • Letwin K, Yee SP, Pawson T. Novel protein-tyrosine kinase cDNAs related to fps/fes and eph cloned using anti-phosphotyrosine antibody. Oncogene. 1988 Dec;3(6):621–627. [PubMed]
  • Lewin B. Driving the cell cycle: M phase kinase, its partners, and substrates. Cell. 1990 Jun 1;61(5):743–752. [PubMed]
  • Lundgren K, Walworth N, Booher R, Dembski M, Kirschner M, Beach D. mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2. Cell. 1991 Mar 22;64(6):1111–1122. [PubMed]
  • Manova K, Nocka K, Besmer P, Bachvarova RF. Gonadal expression of c-kit encoded at the W locus of the mouse. Development. 1990 Dec;110(4):1057–1069. [PubMed]
  • Matsushime H, Jinno A, Takagi N, Shibuya M. A novel mammalian protein kinase gene (mak) is highly expressed in testicular germ cells at and after meiosis. Mol Cell Biol. 1990 May;10(5):2261–2268. [PMC free article] [PubMed]
  • Meijer D, Hermans A, von Lindern M, van Agthoven T, de Klein A, Mackenbach P, Grootegoed A, Talarico D, Della Valle G, Grosveld G. Molecular characterization of the testis specific c-abl mRNA in mouse. EMBO J. 1987 Dec 20;6(13):4041–4048. [PMC free article] [PubMed]
  • Monk M, McLaren A. X-chromosome activity in foetal germ cells of the mouse. J Embryol Exp Morphol. 1981 Jun;63:75–84. [PubMed]
  • Moran MF, Koch CA, Sadowski I, Pawson T. Mutational analysis of a phosphotransfer motif essential for v-fps tyrosine kinase activity. Oncogene. 1988 Dec;3(6):665–672. [PubMed]
  • Morris NR. Mitotic mutants of Aspergillus nidulans. Genet Res. 1975 Dec;26(3):237–254. [PubMed]
  • Motro B, van der Kooy D, Rossant J, Reith A, Bernstein A. Contiguous patterns of c-kit and steel expression: analysis of mutations at the W and Sl loci. Development. 1991 Dec;113(4):1207–1221. [PubMed]
  • Mutter GL, Grills GS, Wolgemuth DJ. Evidence for the involvement of the proto-oncogene c-mos in mammalian meiotic maturation and possibly very early embryogenesis. EMBO J. 1988 Mar;7(3):683–689. [PMC free article] [PubMed]
  • Nurse P. Universal control mechanism regulating onset of M-phase. Nature. 1990 Apr 5;344(6266):503–508. [PubMed]
  • OAKBERG EF. A description of spermiogenesis in the mouse and its use in analysis of the cycle of the seminiferous epithelium and germ cell renewal. Am J Anat. 1956 Nov;99(3):391–413. [PubMed]
  • Oakley BR, Morris NR. A mutation in Aspergillus nidulans that blocks the transition from interphase to prophase. J Cell Biol. 1983 Apr;96(4):1155–1158. [PMC free article] [PubMed]
  • Orr-Urtreger A, Avivi A, Zimmer Y, Givol D, Yarden Y, Lonai P. Developmental expression of c-kit, a proto-oncogene encoded by the W locus. Development. 1990 Aug;109(4):911–923. [PubMed]
  • Osmani AH, McGuire SL, Osmani SA. Parallel activation of the NIMA and p34cdc2 cell cycle-regulated protein kinases is required to initiate mitosis in A. nidulans. Cell. 1991 Oct 18;67(2):283–291. [PubMed]
  • Osmani AH, O'Donnell K, Pu RT, Osmani SA. Activation of the nimA protein kinase plays a unique role during mitosis that cannot be bypassed by absence of the bimE checkpoint. EMBO J. 1991 Sep;10(9):2669–2679. [PMC free article] [PubMed]
  • Osmani SA, Engle DB, Doonan JH, Morris NR. Spindle formation and chromatin condensation in cells blocked at interphase by mutation of a negative cell cycle control gene. Cell. 1988 Jan 29;52(2):241–251. [PubMed]
  • Osmani SA, Pu RT, Morris NR. Mitotic induction and maintenance by overexpression of a G2-specific gene that encodes a potential protein kinase. Cell. 1988 Apr 22;53(2):237–244. [PubMed]
  • Parker LL, Atherton-Fessler S, Lee MS, Ogg S, Falk JL, Swenson KI, Piwnica-Worms H. Cyclin promotes the tyrosine phosphorylation of p34cdc2 in a wee1+ dependent manner. EMBO J. 1991 May;10(5):1255–1263. [PMC free article] [PubMed]
  • Propst F, Rosenberg MP, Oskarsson MK, Russell LB, Nguyen-Huu MC, Nadeau J, Jenkins NA, Copeland NG, Vande Woude GF. Genetic analysis and developmental regulation of testis-specific RNA expression of Mos, Abl, actin and Hox-1.4. Oncogene. 1988 Mar;2(3):227–233. [PubMed]
  • Sagata N, Oskarsson M, Copeland T, Brumbaugh J, Vande Woude GF. Function of c-mos proto-oncogene product in meiotic maturation in Xenopus oocytes. Nature. 1988 Oct 6;335(6190):519–525. [PubMed]
  • Seger R, Ahn NG, Boulton TG, Yancopoulos GD, Panayotatos N, Radziejewska E, Ericsson L, Bratlien RL, Cobb MH, Krebs EG. Microtubule-associated protein 2 kinases, ERK1 and ERK2, undergo autophosphorylation on both tyrosine and threonine residues: implications for their mechanism of activation. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6142–6146. [PMC free article] [PubMed]
  • Sorger PK, Murray AW. S-phase feedback control in budding yeast independent of tyrosine phosphorylation of p34cdc28. Nature. 1992 Jan 23;355(6358):365–368. [PubMed]
  • Stern DF, Zheng P, Beidler DR, Zerillo C. Spk1, a new kinase from Saccharomyces cerevisiae, phosphorylates proteins on serine, threonine, and tyrosine. Mol Cell Biol. 1991 Feb;11(2):987–1001. [PMC free article] [PubMed]
  • Tan JL, Spudich JA. Developmentally regulated protein-tyrosine kinase genes in Dictyostelium discoideum. Mol Cell Biol. 1990 Jul;10(7):3578–3583. [PMC free article] [PubMed]
  • Tsai LH, Harlow E, Meyerson M. Isolation of the human cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase. Nature. 1991 Sep 12;353(6340):174–177. [PubMed]
  • Babitzke P, Kushner SR. The Ams (altered mRNA stability) protein and ribonuclease E are encoded by the same structural gene of Escherichia coli. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):1–5. [PMC free article] [PubMed]

Articles from The EMBO Journal are provided here courtesy of The European Molecular Biology Organization

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • Gene
    Gene
    Gene links
  • Gene (nucleotide)
    Gene (nucleotide)
    Records in Gene identified from shared sequence links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene
    HomoloGene links
  • MedGen
    MedGen
    Related information in MedGen
  • Nucleotide
    Nucleotide
    Published Nucleotide sequences
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • Protein
    Protein
    Published protein sequences
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links
  • Taxonomy
    Taxonomy
    Related taxonomy entry
  • Taxonomy Tree
    Taxonomy Tree

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...