Interaction of 5-lipoxygenase with cellular proteins.
5-Lipoxygenase (5LO) plays a pivotal role in cellular leukotriene synthesis. To identify proteins interacting with human 5LO, we used a two-hybrid approach to screen a human lung cDNA library. From a total of 1.5 x 10(7) yeast transformants, nine independent clones representing three different proteins were isolated and found to ... specifically interact with 5LO. Four 1.7- to 1.8-kb clones represented a 16-kDa protein named coactosin-like protein for its significant homology with coactosin, a protein found to be associated with actin in Dictyostelium discoideum. Coactosin-like protein thus may provide a link between 5LO and the cytoskeleton. Two other yeast clones of 1.5 kb encoded transforming growth factor (TGF) type beta receptor-I-associated protein 1 partial cDNA. TGF type beta receptor-I-associated protein 1 recently has been reported to associate with the activated form of the TGF beta receptor I and may be involved in the TGF beta-induced up-regulation of 5LO expression and activity observed in HL-60 and Mono Mac 6 cells. Finally, three identical 2.1-kb clones contained the partial cDNA of a human protein with high homology to a hypothetical helicase K12H4. 8 from Caenorhabditis elegans and consequently was named DeltaK12H4. 8 homologue. Analysis of the predicted amino acid sequence revealed the presence of a RNase III motif and a double-stranded RNA binding domain, indicative of a protein of nuclear origin. The identification of these 5LO-interacting proteins provides additional approaches to studies of the cellular functions of 5LO.
Mesh Terms:
Activin Receptors, Type I, Amino Acid Sequence, Animals, Arachidonate 5-Lipoxygenase, Base Sequence, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Carrier Proteins, Cell Line, Cloning, Molecular, Dictyostelium, Endoribonucleases, Fungal Proteins, Gene Library, Genes, Reporter, HL-60 Cells, Humans, Lung, Microfilament Proteins, Molecular Sequence Data, Protein-Serine-Threonine Kinases, Protozoan Proteins, Receptors, Transforming Growth Factor beta, Recombinant Proteins, Saccharomyces cerevisiae, Sequence Alignment, Sequence Homology, Amino Acid, beta-Galactosidase
Activin Receptors, Type I, Amino Acid Sequence, Animals, Arachidonate 5-Lipoxygenase, Base Sequence, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Carrier Proteins, Cell Line, Cloning, Molecular, Dictyostelium, Endoribonucleases, Fungal Proteins, Gene Library, Genes, Reporter, HL-60 Cells, Humans, Lung, Microfilament Proteins, Molecular Sequence Data, Protein-Serine-Threonine Kinases, Protozoan Proteins, Receptors, Transforming Growth Factor beta, Recombinant Proteins, Saccharomyces cerevisiae, Sequence Alignment, Sequence Homology, Amino Acid, beta-Galactosidase
Proc. Natl. Acad. Sci. U.S.A.
Date: Mar. 02, 1999
PubMed ID: 10051563
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