16.4 Receptors Coupled to Transcription Factors

What is the TGF-Beta Receptor Signaling?

1. TGF-beta receptors are dimers of type 1 and 2 polypeptides

2. Type 2 receptors phosphorylates and activates type 1

3. Phosphorylates a SMAD protein

4. phophorylated SMADs form complexes and translocate to the nucleus and activate transcription of target genes

What is Transforming Growth Factor?

A polypeptide growth factor that inhibits animal cell proliferation

& related polypeptides are protein kinases that phosphorylate serine or threonine rather than tyrosine, residues on their substrate proteins 

What are TGF beta receptors (Transforming Growth Factor) made up of?

2 polypeptides

• Type 1

• Type 2

that become associated aftter ligand binding

Signaling for TGF beta receptors?

TGF beta receptors are dimers of Type1 and 2 polypeptides

1. Type 2 receptor phosphorylates and activates type 1

2. Phosphorylates SMAD protein

3. Phosphorylated SMADS form complexes and translocate to the nucleus to activate transcription of target genes

What is NFkB signaling from the TNF receptor?

1. IN the inactive state, homo/heterodimers of NF-kB are bound to LkB in they cytoplasm

2. Activation of tumor necrosis factor (TNF) receptor (3 polypeptide chains) leads to the recruitment of adaptor proteins that activate lkb kinase

3. phosphorylation marks lkB for ubiquitination by b-trcp

4. Causes degradation by proteasome

5. Allows NFk-B to translocate to the nucleus and activate transcription of its target genes

What is the WNT pathway an example of?

Signaling system that activates transription factors by inhibiting their ubiquitination and degradation 

• first in drosophilia

What is WNT

A secreted signaling molecule that stimulates a pathway regulating cell fate during embryonic development

What is the WNT pathway? ABSENCE OF WNT

1. Beta catenin is phosphorylated by GSK-3 in a complex with casein kinase-1, axin, and APC (destruction complex)

2. Leads to beta catenin ubiquitination and degradation

What is WNT pathway in presence of WNT?

1. WNT polypeptides bind to Frizzled and LRP receptors 

2. Leading to recruitment of Dishevelled 

3. Inativation of destruction complex and stabilization of beta catenin 

4. Beta catenin translocates to the nucleus 

5. Forms a complex with TCF transcription factors 

6. Converts them from responses to activators of their target genes 

What is the Notch pathway for?

Signaling pathway controlling cell fate during animal development - cell-to=cell interaection during development

What is the Notch Signaling pathway?

1. Serves as a receptor for direct cell-cell signaling by transmembrane proteins on neighboring cells

2. Binding of Delta leads to proteolytic cleavage of Notch by presenilin as part of gamma secretase complex (including nicastrin, aph-1, and pen-2

3. Releases the notch intracellular domain

4. Translocates to the nucleus and interacts with the CSL transcription factor to induce gene expression

Members of the TGF-beta receptor family are…

Serine/theonine kinases that directly phosphorylate and activate Smad transcription factors

WNT signaling acts by preventing …

degradation of beta catenin, which serves as a transcriptional activator

What does notch signaling translocation to the nucleus activate?

A transcription factor