Abstract
Ser/Thr- and Tyr-Protein kinases constitute a key switch underlying the dynamic nature and graded regulation of signal transduction and pathway activities in cellular organization. Here we describe the identification and characterization of Dusty, a single-copy gene that arose in metazoan evolution and encodes a putative dual Ser/Thr and Tyr protein kinase with unique structural features. Dusty is widely expressed in vertebrates, broadly distributed in the central nervous system, and deregulated in certain human cancers. Confocal imaging of transiently expressed human Dusty-GFP fusion proteins showed a cytoplasmic distribution. Dusty proteins from lower to higher species display an increasing degree of sequence conservation from the N-terminal non-catalytic domain to C-terminal catalytic domain. The non-catalytic region has eight conserved cysteine residues, multiple potential kinase-docking motifs and phosphorylation sites, whereas the catalytic domain is divergent and about equally distant of Ser/Thr and Tyr protein kinases. Homology analyses identified the essential catalytic residues, suggesting that Dusty homologues all possess the enzymatic activity of a protein kinase. Taken together, Dusty is a unique evolutionarily selected group of divergent protein kinases that may play important functional roles in the brain and other tissues of vertebrates.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Blotting, Northern
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COS Cells
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Catalytic Domain / genetics*
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Cell Line
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Cell Line, Tumor
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Chlorocebus aethiops
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Evolution, Molecular*
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Female
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Gene Expression Profiling*
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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HeLa Cells
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Humans
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K562 Cells
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Male
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Mice
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Microscopy, Confocal
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Molecular Sequence Data
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NIH 3T3 Cells
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Phylogeny
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Protein Kinases / genetics*
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Protein Kinases / metabolism
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Receptor-Interacting Protein Serine-Threonine Kinases / genetics*
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Receptor-Interacting Protein Serine-Threonine Kinases / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Sequence Homology, Amino Acid
Substances
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Recombinant Fusion Proteins
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Green Fluorescent Proteins
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Protein Kinases
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Receptor-Interacting Protein Serine-Threonine Kinases
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DSTYK protein, human
Associated data
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GENBANK/AY208850
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GENBANK/AY208851
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GENBANK/AY208852
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GENBANK/AY208853
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GENBANK/AY208854
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GENBANK/AY208855
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GENBANK/AY364232
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GENBANK/AY364233
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GENBANK/AY429674
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GENBANK/AY429675
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GENBANK/AY429676
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GENBANK/AY429677
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GENBANK/AY429678
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GENBANK/AY429679
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GENBANK/AY429680
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GENBANK/AY429681
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GENBANK/AY641092
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GENBANK/AY641093
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GENBANK/AY641094
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GENBANK/AY641095
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GENBANK/AY641096
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GENBANK/DQ013067
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GENBANK/DQ013068
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GENBANK/DQ054504
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GENBANK/DQ341264
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GENBANK/DQ419945
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GENBANK/DQ419946