Cloning and characterization of Hunk, a novel mammalian SNF1-related protein kinase.

We previously identified a novel protein kinase, Hunk, by means of a degenerate PCR screen designed to isolate kinases expressed in the murine mammary gland. We now describe the molecular cloning, chromosomal localization, and activity of this kinase and characterize its spatial and temporal pattern of expression in the mouse. We have isolated a 5.0-kb full-length cDNA clone that contains the 714-amino-acid open reading frame encoding Hunk. Analysis of this cDNA reveals that Hunk is most closely related to the SNF1 family of serine/threonine kinases and contains a newly described SNF1 homology domain. Accordingly, antisera specific for Hunk detect an 80-kDa polypeptide with associated phosphotransferase activity. Hunk is located on distal mouse chromosome 16 in a region of conserved synteny with human chromosome 21q22. During fetal development and in the adult mouse, Hunk mRNA expression is developmentally regulated and tissue-specific. Moreover, in situ hybridization analysis reveals that Hunk expression is restricted to subsets of cells within a variety of organs in the adult mouse. These findings suggest a role for Hunk in murine development.

[1]  D. Botstein,et al.  Mutants of yeast defective in sucrose utilization. , 1981, Genetics.

[2]  N. Copeland,et al.  Organization, distribution, and stability of endogenous ecotropic murine leukemia virus DNA sequences in chromosomes of Mus musculus , 1982, Journal of virology.

[3]  R. Desnick,et al.  Human alpha-galactosidase A: nucleotide sequence of a cDNA clone encoding the mature enzyme. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[4]  M. Kozak An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. , 1987, Nucleic acids research.

[5]  I. Parsa Loss of a Mr 78,000 marker in chemically induced transplantable carcinomas and primary carcinoma of human pancreas. , 1988, Cancer research.

[6]  T. Hunter,et al.  The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. , 1988, Science.

[7]  A. Aurias,et al.  Critical role of the D21S55 region on chromosome 21 in the pathogenesis of Down syndrome. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[8]  M. Carlson,et al.  Molecular analysis of the SNF4 gene of Saccharomyces cerevisiae: evidence for physical association of the SNF4 protein with the SNF1 protein kinase , 1989, Molecular and cellular biology.

[9]  S. Fields,et al.  A novel genetic system to detect protein–protein interactions , 1989, Nature.

[10]  D. E. Levin,et al.  A putative protein kinase gene (kin1+) is important for growth polarity in Schizosaccharomyces pombe. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[11]  S. Desiderio,et al.  Specific expression of a tyrosine kinase gene, blk, in B lymphoid cells. , 1990, Science.

[12]  D. Hardie,et al.  Evidence that AMP triggers phosphorylation as well as direct allosteric activation of rat liver AMP-activated protein kinase. A sensitive mechanism to protect the cell against ATP depletion. , 1991, European journal of biochemistry.

[13]  S. Hanks,et al.  Protein kinase catalytic domain sequence database: identification of conserved features of primary structure and classification of family members. , 1991, Methods in enzymology.

[14]  W. Kolch,et al.  Expression of protein kinase C genes in hemopoietic cells is cell-type- and B cell-differentiation stage specific. , 1991, Journal of immunology.

[15]  M. Kozak,et al.  An analysis of vertebrate mRNA sequences: intimations of translational control , 1991, The Journal of cell biology.

[16]  L. Alhonen,et al.  Human spermidine synthase gene: structure and chromosomal localization. , 1991, DNA and cell biology.

[17]  P. Shewry,et al.  Complementation of snf1, a mutation affecting global regulation of carbon metabolism in yeast, by a plant protein kinase cDNA. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[18]  N. Copeland,et al.  Development and applications of a molecular genetic linkage map of the mouse genome. , 1991, Trends in genetics : TIG.

[19]  J. François,et al.  Deletion of SNF1 affects the nutrient response of yeast and resembles mutations which activate the adenylate cyclase pathway. , 1991, Genetics.

[20]  M. Carlson,et al.  A protein kinase substrate identified by the two-hybrid system. , 1992, Science.

[21]  S. Desiderio,et al.  itk, a T-cell-specific tyrosine kinase gene inducible by interleukin 2. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[22]  M. Kreis,et al.  Structure and expression of a gene from Arabidopsis thaliana encoding a protein related to SNF1 protein kinase. , 1992, Gene.

[23]  H. Schnürch,et al.  Expression of tie-2, a member of a novel family of receptor tyrosine kinases, in the endothelial cell lineage. , 1993, Development.

[24]  J. Delabar,et al.  Molecular Mapping of Twenty-Four Features of Down Syndrome on Chromosome 21 , 1993, European journal of human genetics : EJHG.

[25]  O. Witte,et al.  Bruton's Tyrosine Kinase is a Key Regulator in B‐Cell Development , 1994, Immunological reviews.

[26]  K. Miyazono,et al.  Serine/threonine kinase receptors. , 1994, Progress in growth factor research.

[27]  T. Muranaka,et al.  Characterization of tobacco protein kinase NPK5, a homolog of Saccharomyces cerevisiae SNF1 that constitutively activates expression of the glucose-repressible SUC2 gene for a secreted invertase of S. cerevisiae , 1994, Molecular and cellular biology.

[28]  J. Scott,et al.  Mammalian AMP-activated protein kinase is homologous to yeast and plant protein kinases involved in the regulation of carbon metabolism. , 1994, The Journal of biological chemistry.

[29]  D. Hardie,et al.  Roles of the Snf1/Rkin1/AMP-activated protein kinase family in the response to environmental and nutritional stress. , 1994, Seminars in cell biology.

[30]  H. Sano,et al.  Light and nutritional regulation of transcripts encoding a wheat protein kinase homolog is mediated by cytokinins. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[31]  P. Leder,et al.  neu and ras initiate murine mammary tumors that share genetic markers generally absent in c-myc and int-2-initiated tumors. , 1994, Oncogene.

[32]  C. Disteche,et al.  Down syndrome phenotypes: the consequences of chromosomal imbalance. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[33]  M. Carlson,et al.  A family of proteins containing a conserved domain that mediates interaction with the yeast SNF1 protein kinase complex. , 1994, The EMBO journal.

[34]  F. Conlon,et al.  Identification of novel protein kinases expressed in the myocardium of the developing mouse heart , 1994, Mechanisms of Development.

[35]  L. Alhonen,et al.  Nucleotide sequence of mouse spermidine synthase cDNA. , 1994, DNA sequence : the journal of DNA sequencing and mapping.

[36]  K. Kemphues,et al.  par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed , 1995, Cell.

[37]  P. Distefano,et al.  Receptor tyrosine kinase specific for the skeletal muscle lineage: Expression in embryonic muscle, at the neuromuscular junction, and after injury , 1995, Neuron.

[38]  A. Nairn,et al.  The Regulatory Region of Calcium/Calmodulin-dependent Protein Kinase I Contains Closely Associated Autoinhibitory and Calmodulin-binding Domains (*) , 1995, The Journal of Biological Chemistry.

[39]  Junzhe Xu,et al.  The developmental pattern of Brca1 expression implies a role in differentiation of the breast and other tissues , 1995, Nature Genetics.

[40]  D. Hervé,et al.  Molecular analysis of the multiple Golf α subunit mRNAs in the rat brain , 1995 .

[41]  D. Hardie,et al.  Glucose repression/derepression in budding yeast: SNF1 protein kinase is activated by phosphorylation under derepressing conditions, and this correlates with a high AMP:ATP ratio , 1996, Current Biology.

[42]  J. Rubenstein,et al.  Expression Patterns of Two Murine Homologs ofDrosophila Single-MindedSuggest Possible Roles in Embryonic Patterning and in the Pathogenesis of Down Syndrome , 1996, Molecular and Cellular Neuroscience.

[43]  J. Rubenstein,et al.  Expression Patterns of Two Murine Homologs ofDrosophila Single-MindedSuggest Possible Roles in Embryonic Patterning and in the Pathogenesis of Down Syndrome Volume7,Number 1 (1996), pages 1–16: , 1996, Molecular and Cellular Neuroscience.

[44]  H. Joost,et al.  Molecular cloning and characterization of a novel mammalian protein kinase harboring a homology domain that defines a subfamily of serine/threonine kinases. , 1996, European journal of biochemistry.

[45]  J. Scott,et al.  Characterization of AMP-activated protein kinase beta and gamma subunits. Assembly of the heterotrimeric complex in vitro. , 1996, The Journal of biological chemistry.

[46]  D. Hardie,et al.  Regulation of lipid metabolism by the AMP-activated protein kinase. , 1997, Biochemical Society transactions.

[47]  G. Drewes,et al.  MARK, a Novel Family of Protein Kinases That Phosphorylate Microtubule-Associated Proteins and Trigger Microtubule Disruption , 1997, Cell.

[48]  [Identification of the new protein kinase specifically transcribed in mouse tumors with high metastatic potential]. , 1997, Doklady Akademii nauk.

[49]  M. Kobayashi,et al.  Cloning and analysis of a cDNA encoding a two-domain hemoglobin chain from the water flea Daphnia magna. , 1997, Gene.

[50]  R. Parthasarathy,et al.  Molecular characterization of coding and untranslated regions of rat cortex lithium-sensitive myo-inositol monophosphatase cDNA. , 1997, Gene.

[51]  D. Solter,et al.  New member of the Snf1/AMPK kinase family, Melk, is expressed in the mouse egg and preimplantation embryo , 1997, Molecular reproduction and development.

[52]  M. Drab,et al.  Mammalian homologues of C. elegans PAR-1 are asymmetrically localized in epithelial cells and may influence their polarity , 1997, Current Biology.

[53]  H. Gardner,et al.  Developmental expression of Brca2 colocalizes with Brca1 and is associated with proliferation and differentiation in multiple tissues. , 1997, Developmental biology.

[54]  C. Peng,et al.  Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216. , 1997, Science.

[55]  C. Peng,et al.  C-TAK1 protein kinase phosphorylates human Cdc25C on serine 216 and promotes 14-3-3 protein binding. , 1998, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[56]  L. Chodosh,et al.  Cloning and characterization of Krct, a member of a novel subfamily of serine/threonine kinases. , 1998, Human molecular genetics.

[57]  D. Carling,et al.  Dual regulation of the AMP‐activated protein kinase provides a novel mechanism for the control of creatine kinase in skeletal muscle , 1998, The EMBO journal.

[58]  D. Hardie,et al.  AMP-activated protein kinase: an ultrasensitive system for monitoring cellular energy charge. , 1999, The Biochemical journal.

[59]  D. Hardie,et al.  Roles of the AMP-activated/SNF1 protein kinase family in the response to cellular stress. , 1999, Biochemical Society symposium.

[60]  H. Gardner,et al.  Mammary gland development, reproductive history, and breast cancer risk. , 1999, Cancer research.

[61]  E. Harlow,et al.  Using Antibodies: A Laboratory Manual , 1999 .

[62]  H. Gardner,et al.  Protein kinase expression during murine mammary development. , 2000, Developmental biology.

[63]  H. Gardner,et al.  Cloning, characterization, and chromosomal localization of Pnck, a Ca2+/calmodulin-dependent protein kinase , 2000 .

[64]  G. Wertheim,et al.  Developmental role of the SNF1-related kinase Hunk in pregnancy-induced changes in the mammary gland. , 2000, Development.