1 / 10

Signaling Pathways That Control Gene Activity 14.1 - TGF β Receptors and the Direct Activation of Smads

Signaling Pathways That Control Gene Activity 14.1 - TGF β Receptors and the Direct Activation of Smads. Presented By: Todd Lindsey. TGF β. Extracellular signaling molecules known as Transforming Growth Factor β superfamily.

hasad
Download Presentation

Signaling Pathways That Control Gene Activity 14.1 - TGF β Receptors and the Direct Activation of Smads

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Signaling Pathways That Control Gene Activity14.1 - TGFβ Receptors and the Direct Activation of Smads Presented By: Todd Lindsey

  2. TGFβ • Extracellular signaling molecules known as Transforming Growth Factor β superfamily. • Secreted TGFβ is stored in extracellular matrix as inactive complex of TGFβ precursor bound to Latent TGFβ Binding Protein, or LTBP.

  3. Release of Active TGFβ • Binding of LTBP by matrix protein thrombospondin or cell-surface integrins. • Conformational change in LTBP causes release of active TGFβ.

  4. Smads • Smad proteins function as transcription factors in the TGFβ signaling pathway. • R-Smads (receptor-regulated) • Co-Smads • I-Smads (inhibitory)

  5. TGFβReceptors • Type III TGFβ receptor -Cell Surface Proteoglycan -Binds and concentrates TGFβ near surface of the cell. • Type II TGFβ receptor • Type I TGFβ receptor

  6. TGFβ Signaling Pathway • TGFβ dimer induces formation of complex between Type II and Type I TGFβ receptors. • Type II TGFβ receptor phosphorylates and activates Type I receptor.

  7. TGFβ Signaling Pathway • Type I TGFβ receptor phosphorylates an R-Smad (Smad3). • Phosphorylated R-Smad forms cytosolic complex with co-Smad (Smad4).

  8. TGFβ Signaling Pathway • Smad dimer complex translocates into the nucleus. • A nuclear transcription factor binds to smad complex, forming an activation complex that can bind to the target gene, activating transcription.

  9. Regulation of TGFβ-Smad Signaling Pathway • Negative Feedback Loops ▪Cytosolic proteins, SnoN and Ski block transcription activation by bound Smad complexes. ▪ I-Smads, such as Smad7, blocks the Type I receptors from phosphorylating R-Smad proteins.

  10. References • Lodish, et al. Molecular Cell Biology. W.H. Freeman and Company. New York: 2004. • www.whfreeman.com/lodish

More Related