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TGFβ-Receptor 1/ALK5 NEIL MEHTA BIOL 445.001

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Presentation on theme: "TGFβ-Receptor 1/ALK5 NEIL MEHTA BIOL 445.001"— Presentation transcript:

1 TGFβ-Receptor 1/ALK5 NEIL MEHTA BIOL 445.001 http://www.bcm.edu/pediatrics/cardiology/TGFBR2http://en.wikipedia.org/wiki/TGF_beta_receptor_1

2 CELL SIGNALING PATHWAYS

3 HETERO-TETRAMERIC RECEPTOR COMPLEX FORMS UPON BINDING TO LIGAND (TGFβ) http://en.wikipedia.org/wiki/TGF_beta_signaling_pathway

4 SARA MEDIATES RECEPTOR INTERNALIZATION AND PHOSPHORYLATION OF SMAD2 (R-SMAD) http://en.wikipedia.org/wiki/TGF_beta_signaling_pathway

5 PHOSPOHRYLATED R-SMAD/SMAD4 ENTERS NUCLEUS AND CAUSES TRANSCRIPTION OF DNA http://en.wikipedia.org/wiki/TGF_beta_signaling_pathway

6

7 TGFβ-RECEPTOR 1 INDUCES EPITHELIAL TO MESENCHYMAL TRANSITION (EMT) Valcourt et. al. Mol Biol Cell. 2005 April; 16(4): 1987–2002.

8 TβRI –/– MICE DIE AT MIDGESTATION DUE TO IMPAIRED YOLK SAC CIRCULATION Larson et. al. EMBO J. 2001 April 2; 20(7): 1663–1673.

9 LOH OF TGF-βRI GENE IN PANCREATIC AND BILIARY CANCERS Goggins et. al. Cancer Res 1998;58:5329-5332

10 TREATMENT FOR PANCREATIC CANCER USING A TGFβR-1 INHIBITOR Gaspar et. al. Molecular Pharmacology 2007: (72), 152–161.

11 ROLE OF TGFβ-RECEPTOR I IN OTHER PATHWAYS Lee et. al. EMBO J 2007, 26:3957-3967.

12 REFERENCES Gaspar, Nicholas J., et al. (2007) Inhibition of Transforming Growth Factor β Signaling Reduces Pancreatic Adenocarcinoma Growth and Invasiveness. Molecular Pharmacology, 72(1): 152-161. Goggins, Michael, et al. (1998) Genetic Alterations of the Transforming Growth Factor β Receptor Genes in Pancreatic and Biliary Adenocarcinomas. Cancer Research, 58: 5329-5332. Larsson, Jonas, et al. (2001) Abnormal angiogenesis but intact hematopoietic potential in TGF-β type I receptor-deficient mice. The Embo Journal, 20(7): 1663-1673. Lee, Matt K., et al. (2007) TGF-β activates Erk MAP kinase signaling through direct phosphorylation of ShcA. The Embo Journal, 26(17): 3957–3967. Massague, Joan S. (1998) TGFβ Signal Transduction. Annual Review of Biochemistry, 67: 753-791. Valcourt, Ulrich. (2005) TGF-β and the Smad Signaling Pathway Support Transcriptomic Reprogramming during Epithelial-Mesenchymal Cell Transition. Molecular Biology of the Cell, 16(4): 1987–2002.


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