Characterization of an activated human ros gene.

Birchmeier, Carmen; Birnbaum, Daniel; Waitches, Gayle M.; Fasano, Ottavio; Wigler, Michael

doi:10.1128/mcb.6.9.3109

Cited by 102 publications

(63 citation statements)

References 31 publications

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“…The carboxy-terminal region of the predicted seven less protein shows a high degree of homology with all known protein tyrosine kinase domains but is most closely related to the chicken c-ros (47% homology, in cluding conservative changes; Hafen et al 1987) and human c-ros kinase domains (51% homology; Birchmeier et al 1986). Comparison of the sevenless sequence with the availiable human c-ros sequence (C. Birchmeier and M. Wigler, unpubl.…”

Section: Genes and Development 625mentioning

confidence: 99%

“…The sequence of the amino-terminal region suggests that the sevenless protein may have an unusual orientation in the mem brane; the extracellular domain may be anchored at the amino terminus and carboxyl terminus, producing a large loop in the extracellular domain, with the carboxyterminal kinase domain and a short amino-terminal se quence in the cytoplasm of the cell. The carboxyl ter minus of sevenless is homologous to many known tyro sine kinases but resembles the kinase domain of c-ros most closely (Birchmeier, et al 1986;Neckameyer et al 1986;Hafen et al 1987). Comparison of the sevenless and partially determined human c-ros extracellular do main sequences (C. Birchmeier and M. Wigler, unpubl.…”

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confidence: 99%

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Nucleotide sequence and structure of the sevenless gene of Drosophila melanogaster.

Bowtell¹,

Simon²,

Rubin³

1988

Genes Dev.

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In the Drosopbila melanogaster mutant sevenless, the R7 photoreceptor in each of the repeating units, or ommatidia, of the compound eye fails to form. We have determined the nucleotide sequence and structure of the sevenless transcription unit. Overlapping cDNA clones from an eye imaginal disc library were isolated, and these together with corresponding genomic regions were sequenced. The positions of the major and two minor transcription start sites were mapped. The gene encodes a putative cell-surface receptor, the unmodified form of which is predicted as 288 kD, bearing a cytoplasmic tyrosine kinase domain. Several structural features distinguish sevenless from other tyrosine kinase receptors, most notably the large size of its extracellular domain. Moreover, unlike the insulin or epidermal growth factor (EGF) receptors, a putative amino-terminal signal sequence does not immediately follow the initiating methionine codon. Rather, a 21-amino-acid hydrophobic sequence is found 56 amino acids after the likely initiating methionine codon, suggesting that this sequence may function as an amino-terminal anchor. If so, the sevenless protein would be expected to have its 2001-amino-acid extracellular domain anchored as a loop at either end in the membrane. Finally, we have generated a number of transformant lines that carry either a 16.3-kb genomic fragment that extends -950 bp upstream of the transcription start sites or constructs in which a subset of the introns present in the genomic sevenless DNA have been removed. The degree of rescue of the sevenless mutant phenotype has been assayed in these lines using morphological and behavioral assays.

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Section: Genes and Development 625mentioning

confidence: 99%

mentioning

confidence: 99%

Nucleotide sequence and structure of the sevenless gene of Drosophila melanogaster.

Bowtell¹,

Simon²,

Rubin³

1988

Genes Dev.

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“…Similarly, v-fms, the oncogene of the McDonough strain of feline sarcoma virus (FeSV) is likely to be an allele of the gene encoding the receptor for CSF-1, a mononuclear phagocyte growth factor (3). Five additional oncogenes including v-ros/MCF3 (4,5), v-kit (6), NEU (7), MET (8), and TRK (9) are also likely to be derived from transmembrane receptor loci.…”

Section: Introductionmentioning

confidence: 99%

Identification and biochemical characterization of p70TRK, product of the human TRK oncogene.

Mitra

Martı́n-Zanca²,

Barbacid³

1987

Proc. Natl. Acad. Sci. U.S.A.

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TRK is a human transforming gene generated in a colon carcinoma by a somatic rearrangement that fused a nonmuscle tropomyosin gene to sequences that shared extensive homology with members of the tyrosine-protein kinase supergene family. These sequences are likely to be derived from a transmembrane receptor gene whose putative ligand binding domain has been replaced by tropomyosin. In the present studies, we have expressed the entire coding sequences of the TRK oncogene as well as its protein kinase-related carboxylterminal domain in Escherichia coli. Antisera raised against these bacteria-synthesized TRK polypeptides has allowed us to identify the gene product of the TRK oncogene as a 70-kDa protein.Immunoprecipitates containing p70TK have an associated protein kinase activity specific for tyrosine residues. Moreover, p79TRK is phosphorylated in vivo in serine (75%), threonine (20%), and tyrosine (5%) residues. Finally, immunofluorescence and cellular fractionation studies indicate that p79TRK is preferentially located in the cytoplasmic fraction.

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“…Two independent isolates of transforming ros genes were characterized, the oncogene in the chick retrovirus UR2 and a human isolate identified in a transfection tumorigenicity assay (Neckameyer and Wang 1985 ; 'Corresponding author. Birchmeier et al 1986). Both oncogenes encode truncated proteins that lack a c-Ros-specific extracellular domain.…”

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confidence: 99%

The c-ros tyrosine kinase receptor controls regionalization and differentiation of epithelial cells in the epididymis.

Sonnenberg-Riethmacher¹,

Walter²,

Riethmacher³

et al. 1996

Genes Dev.

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203

146

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The c-ros gene was originally identified in mutant form as an oncogene. The proto-oncogene encodes a tyrosine kinase receptor that is expressed in a small number of epithelial cell types, including those of the epididymis. Targeted mutations of c-ros in the mouse reveal an essential role of the gene in male fertility. Male c-ros -1-animals do not reproduce, whereas the fertility of female animals is not affected. We demonstrate that c-ros is not required in a cell autonomous manner for male germ cell development or function. The gene, therefore, does not affect sperm generation or function in a direct manner. The primary defect in the mutant animals was located in the epididymis, showing that c-ros controls appropriate development of the epithelia, particularly regionalization and terminal differentiation. The epididymal defect does not interfere with production or storage of sperm but, rather, with sperm maturation and the ability of sperm to fertilize in vivo. Interestingly, sperm isolated from c-ros -/ -animals can fertilize in vitro. Our results highlight the essential role of the epididymis in male fertility and demonstrate a highly specific function of the c-ros receptor tyrosine kinase during development of distinct epithelial cells. Tyrosine kinase receptors and their specific ligands can have essential roles during embryonic development and adult physiology. Receptors and ligands often form paracrine signaling systems, therefore providing a molecular basis for the interaction between different cell types. Such interactions are essential for ordered growth, differentiation, and morphogenesis in development and can critically influence homeostasis (Geissler et

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Characterization of an activated human ros gene.

Cited by 102 publications

References 31 publications

Nucleotide sequence and structure of the sevenless gene of Drosophila melanogaster.

Nucleotide sequence and structure of the sevenless gene of Drosophila melanogaster.

Identification and biochemical characterization of p70TRK, product of the human TRK oncogene.

The c-ros tyrosine kinase receptor controls regionalization and differentiation of epithelial cells in the epididymis.

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