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A C Oates

Publications and source records attributed to A C Oates.

24 records · Page 2Linked to original sources
PubMed1998

Embryonic expression and activity of doughnut, a second RYK homolog in Drosophila.

In the Drosophila embryo, a subset of muscles require expression and function of the RYK subfamily RTK gene derailed (drl) for correct attachment. We have isolated a second RYK homolog, doughnut (dnt), from Drosophila. The DNT protein exhibits 60% amino acid identity to DRL, and is structurally as similar to the mammalian RYK proteins as is DRL, indicating an ancient duplication event. dnt is expressed in dynamic patterns in the embryonic epidermis, being found at high level in epithelia adjacent to cells that are invaginating into the interior of the embryo, including ventral furrow, cephalic furrow, fore- and hindgut, optic lobe and tracheal pits. dnt is capable of a partial rescue of the muscle attachment defect of drl-/- embryos, indicating that it encodes a receptor with a related and significantly overlapping biochemical function.

Amino Acid Sequence↗
PubMed1998

Positional cloning of the zebrafish sauternes gene: a model for congenital sideroblastic anaemia.

Many human anaemias are caused by defects in haemoglobin synthesis. The zebrafish mutant sauternes (sau) has a microcytic, hypochromic anaemia, suggesting that haemoglobin production is perturbed. During embryogenesis, sau mutants have delayed erythroid maturation and abnormal globin gene expression. Using positional cloning techniques, we show that sau encodes the erythroid-specific isoform of delta-aminolevulinate synthase (ALAS2; also known as ALAS-E), the enzyme required for the first step in haem biosynthesis. As mutations in ALAS2 cause congenital sideroblastic anaemia (CSA) in humans, sau represents the first animal model of this disease.

5-Aminolevulinate Synthetase↗
PubMed1998

Biomolecular interaction analysis of IFN gamma-induced signaling events in whole-cell lysates: prevalence of latent STAT1 in high-molecular weight complexes.

The basic framework for the JAK/STAT pathway is well documented. Recruitment of latent cytoplasmic STAT transcription factors to tyrosine phosphorylated docking sites on cytokine receptors and their JAK-mediated phosphorylation instigates their translocation to the nucleus and their ability to bind DNA. The biochemical processes underlying recruitment and activation of this pathway have commonly been studied in reconstituted in vitro systems using previously defined recombinant signaling components. We have dissected the Interferon gamma (IFN gamma) signal transduction pathway in crude extracts from wild-type and STAT1-negative mutant cell lines by real-time BIAcore analysis, size-exclusion (SE) chromatography and immuno-detection. The data indicate that in detergent-free cell extracts: (1) the phospho-tyrosine (Y440P)-containing peptide motif of the IFN gamma-receptor alpha-chain interacts directly with STAT1, or STAT1 complexes, and no other protein; (2) non-activated STAT1 is present in a higher molecular weight complex(es) and, at least for IFN gamma-primed cells, is available for recruitment to the activated IFN gamma-receptor from only a subset of such complexes; (3) activated STAT1 is released from the receptor as a monomer.

Amino Acid Sequence↗
PubMed1994

Tyrosine kinase JAK1 is associated with the granulocyte-colony-stimulating factor receptor and both become tyrosine-phosphorylated after receptor activation.

Granulocyte-colony-stimulating factor (G-CSF) stimulates the proliferation and differentiation of cells of the neutrophil lineage by interaction with a specific receptor. Early signal transduction events following G-CSF receptor activation were studied. We detected tyrosine phosphorylation of both the G-CSF receptor and the protein tyrosine kinase JAK1 following G-CSF binding to the human G-CSF receptor. In vitro, the kinase activity of JAK1 was increased by G-CSF stimulation. Coimmunoprecipitation of JAK1 with the G-CSF receptor suggested a physical association which existed prior to G-CSF stimulation.

Animals↗
PubMedDate not supplied

Additional hox clusters in the zebrafish: divergent expression patterns belie equivalent activities of duplicate hoxB5 genes.

The evolution of metazoan body plans has involved changes to the Hox genes, which are involved in patterning the body axis and display striking evolutionary conservation of structure and expression. Invertebrates contain a single Hox cluster whereas tetrapods possess four clusters. The zebrafish has seven unlinked hox clusters, a finding that is difficult to reconcile with the notion that genomic complexity, reflected by Hox cluster number, and morphological complexity are causally linked, as the body plan of the zebrafish is not obviously more complex than that of the mouse or human. Why have the additional hox genes in zebrafish been conserved? To address the role of these additional zebrafish hox genes, we have examined the duplicate hoxB5 genes, hoxB5a, and hoxB5b. Conservation of gene duplicates can occur when one gene acquires a new function (neofunctionalization), or when the ancestral function is divided between the two duplicates (subfunctionalization). hoxB5a and hoxB5b are expressed in distinct domains, and their combined expression domain is strikingly similar to that of single Hoxb5 genes in other species. The biochemical functions encoded by the two genes were studied by overexpression, which resulted in identical developmental defects in the anterior hindbrain and cranial neural crest, suggesting strongly that hoxB5a and hoxB5b have equivalent biochemical properties with respect to early development. From these studies, we conclude that conservation of hoxB5a and hoxB5b is likely the result of division of the ancestral Hoxb5 function between the two genes, without significant changes in biochemical activity. These results suggest a resolution to the conundrum of the extra hox genes and clusters in the zebrafish, since if any of the additional hox genes in the zebrafish are similarly subfunctionalized, they are unlikely to supply novel genetic functions. Thus, the morphological complexity potentially conferred by the majority of additional zebrafish hox clusters may not be substantially greater than that conferred by the four tetrapod clusters.

3' Untranslated Regions↗