tailieunhanh - Báo cáo khoa học: PKA independent and cell type specific activation of the expression of caudal homeobox gene Cdx-2 by cyclic AM

Cdx-2 is a transactivator for the proglucagon gene in pancreatic and intes-tinal endocrine cells. Cdx-2 is also expressed in differentiated intestinal epi-thelia of nonendocrine origin. Cdx-2 –⁄ – mice are embryonic lethal, while Cdx-2 +⁄ – mutants show multiple malfunctions including the formation of intestinal polyps. Within the polyps, the remaining wild type Cdx-2 allele ceases its expression, while the expression of both Cdx-2 and proglucagon in the endocrine cells remains unaltered, indicating that Cdx-2 could be haplo-insufficient for nonendocrine cells, but not for proglucagon pro-ducing endocrine cells | iFEBS Journal PKA independent and cell type specific activation of the expression of caudal homeobox gene Cdx-2 by cyclic AMP Liang Chen1 2 Peixiang Wang1 2 Cristiano F. Andrade1 2 Ian Y. Zhao1 2 Philip E. Dube3 Patricia L. Brubaker3 4 Mingyao Liu1 2 3 and Tianru Jin1 2 4 5 1 Division of Celland Molecular Biology Toronto GeneralResearch Institute University Health Network 2 Institute of MedicalScience University of Toronto Canada 3 Department of Physiology University of Toronto Canada 4 Department of Medicine University of Toronto Canada 5 Department of Laboratory Medicine and Pathobiology University of Toronto Canada Keywords Cdx-2 cAMP Epac ERK1 2 proglucagon Correspondence T. Jin Division of Celland Molecular Biology Toronto GeneralResearch Institute University Health Network. 67 College St. Toronto Ontario M5G 2M1 Fax 1 416 340 3453 Tel 1 416 340 4800 ext. 4768 E-mail Received 4 March 2005 accepted 31 March 2005 doi Cdx-2 is a transactivator for the proglucagon gene in pancreatic and intestinal endocrine cells. Cdx-2 is also expressed in differentiated intestinal epithelia of nonendocrine origin. Cdx-2 mice are embryonic lethal while Cdx-2 mutants show multiple malfunctions including the formation of intestinal polyps. Within the polyps the remaining wild type Cdx-2 allele ceases its expression while the expression of both Cdx-2 and proglucagon in the endocrine cells remains unaltered indicating that Cdx-2 could be haplo-insufficient for nonendocrine cells but not for proglucagon producing endocrine cells. We propose that mechanisms underlying Cdx-2 expression and auto-regulation Xu F Li H Jin T 1999 J Biol Chem 274 34310-34316 differ in these two types of cells. We show here that forskolin and cAMP upregulate Cdx-2 expression in proglucagon producing cells but not in colon cancer cells and primary intestinal cell cultures. It is unlikely that the activation is mainly mediated by PKA because the activation

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