Identification of mouse ULK1, a novel protein kinase structurally related to C. elegans UNC-51.

A novel protein kinase related to the C. elegans serine/threonine kinase UNC-51 was cloned from mouse. The UNC-51-Like Kinase (ULK)1 is encoded by a cDNA of 1051 amino acids with calculated MW of 113 kDa. Comparison of the ULK1 and UNC-51 shows the highest conservation in the amino-terminal kinase domain, which is followed by a proline/serine-rich (PS) domain and a conserved carboxyl-terminal (C) domain. ULK1 mRNA is expressed in various tissues, and is mapped to mouse chromosome 5F and rat chromosome 12q16.3, by fluorescent in situ hybridization. HA-tagged ULK1 is expressed as a protein of approximately 150 kDa in COS7 cells and is auto-phosphorylated in vitro in its PS domain. We propose that ULK1, UNC-51 and a yeast protein kinase Apg1p comprise a novel subfamily of protein kinase, which is structurally conserved among eukaryotes.

[1]  D. Riddle.  C. Elegans II , 1998 .

[2]  D. Lipman,et al.  A genomic perspective on protein families. , 1997, Science.

[3]  Y. Ohshima,et al.  The UNC-14 protein required for axonal elongation and guidance in Caenorhabditis elegans interacts with the serine/threonine kinase UNC-51. , 1997, Genes & development.

[4]  A. Matsuura,et al.  Apg1p, a novel protein kinase required for the autophagic process in Saccharomyces cerevisiae. , 1997, Gene.

[5]  Stefan A. Przyborski,et al.  The mouse rostral cerebellar malformation gene encodes an UNC-5-like protein , 1997, Nature.

[6]  M. Masu,et al.  Vertebrate homologues of C. elegans UNC-5 are candidate netrin receptors , 1997, Nature.

[7]  T. Hunter,et al.  The protein kinases of budding yeast: six score and more. , 1997, Trends in biochemical sciences.

[8]  J. Culotti,et al.  UNC-40, a C. elegans Homolog of DCC (Deleted in Colorectal Cancer), Is Required in Motile Cells Responding to UNC-6 Netrin Cues , 1996, Cell.

[9]  Fumio Nakamura,et al.  Collapsin-induced growth cone collapse mediated by an intracellular protein related to UNC-33 , 1995, Nature.

[10]  V. Wheaton,et al.  An ankyrin-related gene (unc-44) is necessary for proper axonal guidance in Caenorhabditis elegans , 1995, The Journal of cell biology.

[11]  V. Chapman,et al.  Application of fluorescence in situ hybridization in genome analysis of the mouse , 1995, Electrophoresis.

[12]  I. Mori,et al.  Caenorhabditis elegans unc-51 gene required for axonal elongation encodes a novel serine/threonine kinase. , 1994, Genes & development.

[13]  T. Jessell,et al.  The netrins define a family of axon outgrowth-promoting proteins homologous to C. elegans UNC-6 , 1994, Cell.

[14]  H. Horvitz,et al.  Genes necessary for directed axonal elongation or fasciculation in C. elegans , 1992, Neuron.

[15]  V. Chapman,et al.  Location of the mouse complement factor H gene (cfh) by FISH analysis and replication R-banding. , 1992, Cytogenetics and cell genetics.

[16]  M. Lyon,et al.  Genetic variants and strains of the laboratory mouse , 1989 .

[17]  H. Horvitz,et al.  A genetic pathway for the development of the Caenorhabditis elegans HSN motor neurons , 1988, Nature.

[18]  K. Arai,et al.  SR alpha promoter: an efficient and versatile mammalian cDNA expression system composed of the simian virus 40 early promoter and the R-U5 segment of human T-cell leukemia virus type 1 long terminal repeat , 1988, Molecular and cellular biology.