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Biomedical subjects

B Dickson

Publications and source records attributed to B Dickson.

6 recordsLinked to original sources

Raf functions downstream of Ras1 in the Sevenless signal transduction pathway.

Specification of the R7 cell fate in the developing Drosophila eye requires activation of the Sevenless (Sev) receptor tyrosine kinase, located on the surface of the R7 precursor cell, by its interaction with the Boss protein, expressed on the surface of the neighbouring R8 cell. Four genes that participate in the intracellular transmission of this signal have so far been identified and molecularly characterized: Ras1, Sos, Gap1 and sina (refs 4-8). The Drosophila homologue of the mammalian Raf-1 serine/threonine kinase, which has been implicated in signal transduction pathways activated by many receptor tyrosine kinases (reviewed in refs 9 and 10), is encoded by the raf locus (also known as l(1)polehole, Draf-1 or Draf). Here we show that the Drosophila Raf serine/threonine kinase also plays a crucial role in the R7 pathway: the response to Sev activity is dependent on raf function, and a constitutively activated Raf protein can induce R7 cell development in the absence of sev function. We also present genetic evidence suggesting that Raf acts downstream of Ras1 and upstream of Sina in this signal transduction cascade.

Animals

Embryonal sarcoma of the liver in an adult treated with preoperative chemotherapy, radiation therapy, and hepatic lobectomy.

A rare case of embryonal sarcoma of the liver in a 28-year-old man is reported. The patient was treated preoperatively with a combination of chemotherapy and radiation therapy. Complete surgical resection, 4.5 months after diagnosis, consisted of a left hepatic lobectomy. No viable tumor was found in the operative specimen. The patient was disease-free 20 months postoperatively.

Adult

Prepattern in the developing Drosophila eye revealed by an activated torso--sevenless chimeric receptor.

Induction of the R7 photoreceptor cell fate in the developing eye of Drosophila depends on the activation of the sevenless receptor tyrosine kinase in the R7 precursor cell. The sevenless protein is expressed transiently in 8 of the 20 precursors of an ommatidium. Activation of the sevenless kinase in these eight cells indicates that six of them are competent to become R7 cells. To test the competence of all 20 ommatidial precursors in a temporally unrestricted manner we have used a constitutively activated sevenless kinase created by fusing the extracellular domain of a mutant torso protein, another Drosophila receptor tyrosine kinase, to the sevenless kinase. Our results show that competence to develop as neuronal cells in response to sevenless activity is spatially and temporally limited to the cells expressing sevenless. Therefore, the expression of sevenless marks a preexisting pattern of developmental potential in the disc epithelium.

Animals

Importance of the position of TYR R boxes for repression and activation of the tyrP and aroF genes in Escherichia coli.

Tyrosine-mediated repression of aroF and tyrP was studied by inserting DNA sequences between the two adjacent TYR R boxes which, in each case, overlap the respective RNA polymerase binding sites of these genes. In both cases, repression was greatest when homologous regions of these two TYR R boxes were on the same face of the DNA helix and the boxes were directly adjacent. An insertion of 3 bases was sufficient to abolish repression, which was reestablished as the boxes became separated by one full turn of the helix. These observations, coupled with the results of in vitro DNase I protection studies, supported the hypothesis that the binding of TyrR protein to the downstream boxes required cooperative interaction with TyrR protein already bound to the upstream boxes. In the case of tyrP, moving the upstream box also affected activation. Maximal activation was observed when the box was moved 3 or 12 to 14 residues upstream. Practically no activation was seen at intermediate positions, such as +7 and -4. It is hypothesized that these results indicate positions allowing maximal interaction between TyrR protein bound to the upstream box and RNA polymerase bound to the RNA polymerase binding site.

Base Sequence