TGFbeta signaling

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TGF-beta signaling
Roberts, et al., 2000. Signaling from TGF-b
receptors. From Signaling networks and cell cycle
control, Ed. S. Gutkind, Humana press, NJ, pp.
39-51. Derynck, et al., 2001. TGF-b signaling in
tumor suppression and cancer progression. Nature
Genetics 29117-129. Akhurst, R. Derynck, R.
2001. TGF-b signaling in cancer-a double edged
sword. Trends Cell Biol. 11S44-S50. Schuster
Kreiglstein, 2002. Mechanisms of TGFb-mediated
apoptosis. Cell Tissue Res. 3071-14. Massague,
J. and Wotton, D. 2000. Transcriptional control
by the TGF-b/Smad signaling system. EMBO Journal
191745-1754. Piek, et al., 1999. Specificity,
diversity, and regulation in TGF-b superfamily.
FASEB J. 132105-2124. Luo, et al., 1999. The ski
oncoprotein interacts with the Smad protein to
repress TGF beta signaling. Genes Dev.
132196-2206. Wotton D, Massague J. Smad
transcriptional corepressors in TGF beta family
signaling. Curr Top Microbiol Immunol.
2001254145-64. Stroschein SL, Wang W, Zhou S,
Zhou Q, Luo K. Negative feedback regulation of
TGF-beta signaling by the SnoN oncoprotein.Scienc
e. 1999 Oct 22286(5440)771-4. Itoh et al.,
2000. Signaling of transforming growth factor b
family through Smad ptoteins. Eur. J. Biochem.
2676954-6967.
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Common Protein Kinases Regulating Signal
Transduction
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Transforming Growth Factor beta Family
BMP2 subfamily Gastrulation, neurogenesis,
chondrogenesis, interdigital apoptosis,
mesoderm patterning BMP5 subfamily Development,
neurogenesis GDF5 subfamily Chondrogenesis in
developing limbs BMP3 subfamily Osteogenic
differentiation, monocyte chemotaxis Activin
subfamily FSH production, erythroid cell
differentiation, mesoderm induction
(frog) TGF-beta subfamily cell cycle arrest in
epithelial and hematopoietic cells,
mesenchymal cell proliferation and
differentiation, wound healing, ECM
production and modulation, angiogenesis,
chemotaxis, invasion, immunosuppression,
apoptosis
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Activation of latent TGFbeta
LAP latency associated peptide
(TGFb-prepeptide) LTBP latent TGFb binding
protein
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Type I and II TGFbeta Receptor Families
Ligand binding
Signal transducing
From Massague, 1998. Ann Rev Biochem. 67753-791.
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TGF-b Activation
SARA Smad anchor for receptor activation
Piek et al., 1999. FASEB J. 132105-2124
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SMADs

• R-SMADs, receptor activated, signal transducing
  1,2,3,5,8,9
• Co-SMADs, common mediator Smad4/DPC4
• I-SMADs, Inhibitory 6,7,
• Xsmad 8

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Akhurst Dernyck, 2001. Trends Cell Biol.
11S44-S51.
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Smad Domains and their Functions
SBE SMAD binding element
From Massague, 1998. Ann Rev Biochem. 67753-791.
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Smads
SAD
Roberts, et al., 2000. pp39-51. From Signaling
networks and cell cycle control. Ed. S. Gutkind,
Human Press, NJ.
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Wrana, 2000 Cell 100189
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TGF beta signaling controls gene transcriptopn
Cell cycle arrest ECM synthesis
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Sno and Ski block TGFb pathway
SkiSloan Kettering Institute SnoSki related gene
Stroschen et al., 1999. Science 286771-774. Song
et al., 1999. PNAS 9611774-11781.
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Ingman and Robertson, 2002. BioEssays 24904-914.
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Nuclear Partners for Smads
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Smads as signal regulators
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TGF-b signaling in tumor suppression and cancer
progression. Dernyck et al., 2001
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Mechanism of TGF-b mediated apoptosis. Schuster
Krieglstein, 2002. Cell Tissue Res. 3071-14.
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