Biomedical subjects

G Q Daley

Publications and source records attributed to G Q Daley.

40 records · Page 3Linked to original sources

PubMed1986

The chronic myelogenous leukemia-specific P210 protein is the product of the bcr/abl hybrid gene.

Chronic myelogenous leukemia (CML) is a human disease associated with a consistent chromosomal translocation that results in sequences from the c-abl locus on chromosome 9 being fused to sequences in a breakpoint cluster region (bcr) on chromosome 22. CML cells have two novel products: an 8.5-kilobase RNA transcript containing both abl and bcr and a 210-kilodalton phosphoprotein (P210) recognized by v-abl-specific antisera. To test whether the P210 is the product of the novel 8.5-kilobase bcr/abl fusion transcript, antibodies were prepared against c-abl and bcr determinants. By using these reagents and v-abl-specific antisera, it was demonstrated that the P210 in CML cells is indeed the protein product of the 8.5-kilobase transcript. By analogy to the gag/abl fusion protein of Abelson murine leukemia virus, the replacement of amino terminal c-abl sequences by bcr sequences in P210 may create a transforming protein involved in CML. A 190-kilodalton phosphoprotein that is a candidate for the normal bcr protein was identified in both HeLa and K562 cells.

Abelson murine leukemia virus↗

PubMed1986

Alternative 5' exons in c-abl mRNA.

The cellular abl proto-oncogene encodes a protein-tyrosine kinase and is expressed in many cell types in two or three mRNA size species. Four types of mouse c-abl cDNAs have been cloned from 70Z/3 lymphoid cells that have different 5' sequences encoding predicted N-terminal regions of 20-45 amino acids. One of the four cDNAs has a predicted N-terminal sequence of met-gly-gln in common with the gag N terminus of v-abl. The 5' heterogeneity appears to be generated by alternative addition of 5' exons onto a common set of 3' exons. Alternative splicing occurs at the same site at which bcr sequences join to abl sequences in the Philadelphia chromosome translocation.

Amino Acid Sequence↗

PubMed1986

Overlapping cDNA clones define the complete coding region for the P210c-abl gene product associated with chronic myelogenous leukemia cells containing the Philadelphia chromosome.

The Philadelphia chromosome, observed in greater than 90% of patients with chronic myelogenous leukemia, results from a reciprocal translocation between chromosomes 9 and 22. The translocation breakpoint on chromosome 9 occurs near the ABL gene and correlates with the production of a chronic myelogenous leukemia-specific 8.5-kilobase ABL-related mRNA species accompanied by a structurally altered ABL protein (P210c-abl). The N-terminal sequence of the protein is derived from the BCR gene on chromosome 22. We have isolated overlapping cDNA clones from the K-562 cell line corresponding to approximately 8.5 kilobases of mRNA and have sequenced 2550 nucleotides at the 5' end. Our results indicate that the 5' end of the 8.5-kilobase mRNA consists of greater than 400 nucleotides of noncoding sequence that are greater than 80% G + C rich. Based on our sequence analysis, we propose that initiation of translation occurs at nucleotide 471, such that the initial 927 amino acids of P210c-abl are derived from BCR sequences. Our cDNA clones thus define the complete coding sequences for the P210c-abl gene product.

Base Sequence↗

PubMed1986

Isolation of chicken cellular DNA sequences with homology to the region of viral oncogenes that encodes the tyrosine kinase domain.

A library of chicken genomic DNA was screened for sequences that could hybridize to a cloned DNA fragment containing the transforming gene (v-fps) of Fujinami sarcoma virus. In addition to c-fps, two unique chicken cellular DNA sequences were isolated that hybridized weakly to v-fps. These sequences hybridized with many other viral oncogenes encoding tyrosine kinases. Sequence analysis of the region where homology was detected revealed a region that is highly conserved among the tyrosine kinases both at the nucleotide and amino acid levels. Although we were unable to detect expression of either chicken cellular DNA sequence in a variety of avian tissues, the data suggest the existence of additional members of the tyrosine kinase gene family. Screening genomic libraries for sequences that hybridize weakly to functional regions of other genes may prove useful for the isolation and characterization of additional members of other gene families.

Animals↗