Molecular cloning of the ets proto-oncogene of the sea urchin and analysis of its developmental expression

Chen, Zhang-qun; Kan, Nancy C.; Pribyl, Louis J.; Lautenberger, James A.; Moudrianakis, Evangelos N.; Papas, Takis S.

doi:10.1016/0012-1606(88)90224-2

Cited by 45 publications

(17 citation statements)

References 28 publications

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“…Recently, the equivalent of the human ETS2 gene has been identified in chicken (14). The ets-related sequences in Drosophila (15), sea urchin (16), and Xenopus (Z. Q. Chen and L. A. Burdett, personal communication) have been isolated and characterized. In this paper we describe the predicted gene products of the human ETS) and ETS2 genes and mouse Ets-2 gene.t We will compare the conserved protein domains encoded by these genes to the chicken protooncogene and to the ets-related coding sequences of other species such as Xenopus, sea urchin, and Drosophila.…”

mentioning

confidence: 99%

Mammalian ets-1 and ets-2 genes encode highly conserved proteins.

Watson

McWilliams

Lapis

et al. 1988

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

224

138

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Cellular ets sequences homologous to v-ets of the avian leukemia virus E26 are highly conserved. In mammals the ets sequences are dispersed on two separate chromosomal loci, called ets4 and ets-2. To determine the structure of these two genes and identify the open reading frames that code for the putative proteins, we have sequenced human ets-) cDNAs and ets-2 cDNA clones obtained from both human and mouse. The human ETS) gene is capable of encoding a protein of 441 amino acids. This protein is >95% identical to the chicken c-ets-1 gene product. Thus, the human ETS) gene is homologous to the chicken c-ets-1 gene, the protooncogene that the E26 virus transduced. Human and mouse ets-2 cDNA clones are closely related and contain open reading frames capable of encoding proteins of 469 and 468 residues, respectively. Direct comparison of these data with previously published findings indicates that ets is a family of genes whose members share distinct domains.

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mentioning

confidence: 99%

Mammalian ets-1 and ets-2 genes encode highly conserved proteins.

Watson

McWilliams

Lapis

et al. 1988

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

224

138

View full text Add to dashboard Cite

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“…The cellular homologs of the v-ets sequence constitute the ets gene family which includes ets-1, ets-2, erg, elk-i, and elk-2 (4, [16][17][18]22). The functional importance of the gene family is suggested by the fact that it is highly conserved in a wide range of phylogeny, from drosophila to humans (5,15,21). Nuclear proteins of about 60 kilodaltons were previously identified as the products of the human and chicken ets-2 genes (4, 8).…”

mentioning

confidence: 99%

Phosphorylation of the ETS-2 protein: regulation by the T-cell antigen receptor-CD3 complex.

Fujiwara¹,

Koizumi²,

Fisher³

et al. 1990

Mol. Cell. Biol.

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Phosphorylation of the human ets-2 protein in response to mitogenic signals to T lymphocytes was investigated in Jurkat cells. Activation of the cells by antibodies against the T-cell antigen receptor-CD3 complex or by concanavalin A was followed within 5 min by increased phosphorylation of the protein, as shown by a mobility shift of the protein from 54 to 56 kilodaltons in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and increased incorporation of 32p. The Ca2" ionophores A23187 and ionomycin were able to mimic this effect, suggesting that this phosphorylation is mediated by Ca2+.The retroviral oncogenes were derived from cellular genes, termed proto-oncogenes, which are normally involved in the signaling systems regulating various cellular functions, including proliferation and differentiation (23). The avian retrovirus E26 contains two cell-derived sequences, v-mybE and v-ets, and both of them are involved in cellular transformation by the virus (9,(11)(12)(13)25). The cellular homologs of the v-ets sequence constitute the ets gene family which includes ets-1, ets-2, erg, elk-i, and elk-2 (4, [16][17][18]22). The functional importance of the gene family is suggested by the fact that it is highly conserved in a wide range of phylogeny, from drosophila to humans (5,15,21). Nuclear proteins of about 60 kilodaltons were previously identified as the products of the human and chicken ets-2 genes (4, 8). The ets-2 proteins are similar to other nuclear proto-oncogene products with respect to quick turnover, phosphorylation, and modulation of expression by external stimuli (2, 4, 7).In our attempt to find a possible association between the ets-2 protein and the cellular signaling systems, we have been characterizing the posttranslational modification of ets-2 protein in response to the intracellular second messengers. Ca2+ and protein kinase C are particularly interesting because they have essential roles in the regulation of Tlymphocyte functions (10,20,24), and high expression of the ets-2 protein in the thymus suggests that it has a role in these T-cell regulatory processes (2, 3). We have previously reported that activation of protein kinase C stabilizes the labile ets-2 protein (7). Here we present evidence that the phosphorylation of the ets-2 protein in a human T-cell line is stimulated by mitogenic signals mediated by a Ca2+-mediated mechanism.We chose the human mature T-cell line Jurkat for our investigation because this cell line has been well characterized as a model system to study early signaling mechanisms in T-cell activation. Jurkat cells were labeled with [35S] methionine or 32p;, and the cellular lysate was immunoprecipitated by ets-2-specific polyclonal or monoclonal antibodies raised against a bacterially expressed human ets-2 protein (7, 8). The results (Fig. 1A) (p56) and a sharp 54-kilodalton band (p54), as fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These two components were competed out by the bacterially expressed human ets-2 protein which was u...

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“…Drosophila melanogaster and Lytechinas variegatus (sea urchin) have ets-2 genes, and their 3' domains have more than 90% identity of amino acid sequences when compared with the corresponding domain of the human ets-2 gene (7,41). This high degree of conservation indicates that the ets-2 gene has an essential function in cells.…”

mentioning

confidence: 99%

A short-lived nuclear phosphoprotein encoded by the human ets-2 proto-oncogene is stabilized by activation of protein kinase C.

Fujiwara¹,

Fisher²,

Bhat³

et al. 1988

Mol. Cell. Biol.

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The human ets-2 gene is a homolog of the v-ets oncogene of the E26 virus and codes for a 56-kilodalton nuclear protein. The ets-2 protein is phosphorylated and has a rapid turnover, with a half-life of 20 min. When human lymphocytic CEM cells were treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), the level of the ets-2 protein was quickly elevated 5-to 20-fold. This effect of TPA was mimicked by a synthetic diacylglycerol, 1-oleoyl-2-acetyl glycerol, and was blocked by the protein kinase C inhibitor 117, indicating that protein kinase C is involved in the induction. The increase in the ets-2 protein was due to stabilization of the protein, because the protein had a half-life of more than 2 h in the presence of TPA and the ets-2 mRNA level did not increase significantly upon TPA treatment. The protein synthesis inhibitor cycloheximide enhanced the effect of TPA on the ets-2 protein and could itself slow turnover of the protein.Properties of the ets-2 protein, such as nuclear localization, phosphorylation, rapid turnover, and response to protein kinase C, indicate that this protein belongs to a group of oncogene proteins which are generally thought to have regulatory functions in the nucleus (e.g., myc, fos, myb, and p53). Our results suggest that protein kinase C, either directly or indirectly, regulates the level of the ets-2 protein by posttranslational mechanisms.

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Molecular cloning of the ets proto-oncogene of the sea urchin and analysis of its developmental expression

Cited by 45 publications

References 28 publications

Mammalian ets-1 and ets-2 genes encode highly conserved proteins.

Mammalian ets-1 and ets-2 genes encode highly conserved proteins.

Phosphorylation of the ETS-2 protein: regulation by the T-cell antigen receptor-CD3 complex.

A short-lived nuclear phosphoprotein encoded by the human ets-2 proto-oncogene is stabilized by activation of protein kinase C.

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