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The Gene Encoding the Mitogen-responsive Phosphoprotein Dab2 Is Differentially Regulated by GATA-6 and GATA-4 in the Visceral Endoderm

Morrisey, Edward E., Musco, Simone, Chen, Mary Y.Z., Lu, Min Min, Leiden, Jeffrey M., Parmacek, Michael S.·2000·Journal of Biological Chemistry
DOI 10.1074/jbc.m001331200
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Abstract

Gene targeting studies have demonstrated that the zinc finger transcription factor GATA-6 lies upstream in a transcriptional cascade that controls differentiation of the visceral endoderm. To understand the function of GATA-6 in the visceral endoderm and to identify genes regulated by GATA-6 in this tissue, subtractive hybridization was performed using template cDNAs derived from differentiated wild-type embryonic stem (ES) cells and GATA-6(-/-) ES cells, respectively. These analyses revealed that the gene encoding Dab2, a mitogen-responsive phosphoprotein, is differentially expressed in wild-type and GATA-6-deficient ES cells. Consistent with these findings, Dab2 is expressed in the visceral endoderm of wild-type embryos but not in the visceral endoderm of GATA-6-deficient embryos. Cotransfection experiments demonstrate that the human Dab2 promoter can be transactivated by forced expression of GATA-6 in NIH-3T3 cells. In contrast, forced expression of GATA-4 does not transactivate the human Dab2 promoter and Dab2 is expressed in the visceral endoderm of GATA-4 null embryos. Surprisingly, the specificity of GATA-6-induced transactivation of the Dab2 promoter is not mediated through its zinc finger DNA-binding domain. Taken together, these data demonstrate that the mitogen-responsive phosphoprotein Dab2 is a downstream target of GATA-6 in the visceral endoderm. Moreover, these data demonstrate that molecular mechanisms have evolved that direct, and distinguish, the functional…

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Crossref · 10.1074/jbc.m001331200

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  • Dab2 is involved in cell positioning and formation of the visceral endoderm during mouse embryogenesis.

    “Dab2, one of two mammalian orthologs of Drosophila Disabled, has been shown to be involved in cell positioning and formation of visceral endoderm during mouse embryogenesis, but its role in neuronal development is not yet fully understood.”

    From Dynamic expression of Dab2 in the mouse embryonic central nervous system (2008) · cites this paper as [23]

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Metadata

Authors
Morrisey, E. E., Musco, S., Chen, M. Y. Z., Lu, M. M., Leiden, J. M., & Parmacek, M. S.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2000-06
Volume
275
Issue
26
Pages
19949-19954
ISSN
0021-9258
DOI
10.1074/jbc.m001331200
Cited by
76
References
2
Language
en
Licence

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