Chapter 16 - Signaling Pathways That Control Gene Expression
16.1 Receptor Serine Kinases That Activate Smads
The transforming growth factor β (TGF-β) family inhibits cell proliferation and regulates development.
Three types of TGF-β receptors activate Smads.
Smads interact with regulatory DNA sequences at sites adjacent to those occupied by cell-specific master transcription factors to induce target genes cell-specifically.
TGF-β/Smad Signaling Pathway
(a) Mature dimeric TGF-β:
Shows the mature dimeric form of TGF-β.
(b) Exterior TGF-β:
RIII: A type of TGF-β receptor.
RII: Another type of TGF-β receptor that interacts with TGF-β.
RI: A third type of TGF-β receptor.
1a & 1b: Initial steps in the pathway.
Cytosol: The location of several key events.
Smad2/3: A type of Smad protein.
Contains a Nuclear Localization Signal (NLS).
Also contains MH2 and MH1 domains.
3: Smad2/3 becomes phosphorylated (Smad2/3-P).
Smad4: Another Smad protein.
Also contains MH2 and MH1 domains and NLS.
Imp-β: Importin-beta, involved in nuclear import.
10: A phosphatase removes the phosphate group from Smad2/3-P.
Nucleus: Where transcription regulation occurs.
Smad2/3-P: Phosphorylated Smad2/3 enters the nucleus.
Smad4: Smad4 also enters the nucleus.
Ran: A GTPase involved in nuclear transport.
6: Step involving Ran.
STP: Something related to the signaling process.
TFE3: A transcription factor.
8: Phosphorylation step (P).
Co-activators: Proteins that enhance transcription.
Transcription: The process of gene expression.
AGACCACGTG PAI-1 JAYAY: DNA sequence.
3-bp spacer: A three base pair spacer in the DNA sequence.