Signaling Pathways Flashcards
Signal transduction pathways:
- are established when a ligand binds to a receptor
- result in a signal being transmitted to the nucleus of a responding cell
- responding cell produces gene products that influence the developmental pathway of the cell
What are some signaling factor families discussed in lecture?
- transforming growth factor beta superfamily
- fibroblast growth factor family
- hedgehog family
- Wnt family
What is the structure of transforming growth factor beta superfamily (TGF-beta1)?
- disulfide linked dimer
- synthesized as a pair of inactive 390 aa precursors -> large pro region and bio active region
- proregion is cleaved from the bioactive region
- 2 bioactive regions and 2 proregions are secreted
- bioactive regions form a dimer
- proregion complex and bioactive dimer maintain the latent form
- activation occurs when the proregion said are separated from the bioactive dimer
- bioactive is signaling molecule
Function of the bone morphogenic proteins. (TGF)
-15 members
-inhibit other processes in the embryo
-often act by being inhibited by other molecules
+bind to bioactive dimers
How do fibroblast growth factors functions?
-22 members
- modification of interaction with heparin proteoglycans in the receptor complex
- regulation at membrane of responding cell via actions of transmembrane proteins
- regulation by various molecules that complex with various parts of signal transduction machinery
What other molecule is hedgehog family related to?
- segment polarity gene in Drosophila
- include: desert, Indian, SHH
How many members of the Wnt family? What is it related to?
- 18 members
- related to segment polarity gene in Drosophilia
- often interacts with components of extracellular matrix
- plays different roles in various vertebrates
What are receptor molecules?
-intracellular receptors
-cell surface receptors:
+receptors with intrinsic protein kinase activity
+receptors that utilize a second messenger system
How does the protein kinase receptor molecule act on fibroblast growth factors and TGF factors?
Fibroblast:
-cytoplasmic domain possesses tyrosine kinase activity
- TGF:
- cytoplasmic domain possesses serine/threonine kinase activity
What are the actions of delta-notch pathway?
- delta on dominant cell
- Notch receptor on neighboring cell
- proteolytic cleavage of Notch intracellular domain
- Notch complexes with Deltex
- complex enters nucleus and binds to suppressor of hairless
- notch-Deltex-suppressor on hairless complex binds to enhancer of split
- resultant inhibitory signal represses gene expression
How does the signaling for lateral inhibition work?
- dominant cell expresses Delta on its membrane
- Delta binds to Notch receptors on neighboring cells and represses genes in the neighboring cells
Summarize the receptor tyrosine kinase pathway.
Fibroblast:
- FGF binds to receptor tyrosine kinase
- G protein is activated which leads to activation of pathway components: RAS, RAF, MAP kinase, and ERK
- ERK translocateds to nucleus and activates various transcription factors
TGF:
- TGF binds to serine/threonine kinase receptor type II
- receptor type II dimerizes with receptor type I and activates R-Smad and Co-Smad (dimerize)
- Smad dimer translocates to nucleus and binds to cofactors which can then bind to DNA regulatory factors
Outline the hedgehog pathway.
- SHH is complexed with cholesterol after being translated
- SHH-cholesterol is translocated to cell surface via Dispersed
- SHH inhibits the inhibitory actions of Patched and Smoothened on target cell
- uninhibited Smoothened signals the release of transcription Gli from a complex of microtubules
- Gli translocates to the nucleus and influences gene expression
Outline the Wnt signaling pathway.
-in absence of Wnt, beta-catenins are bound to intracellular destruction complex within the target cell
- Wnt binds to Frizzled to target cell
- Frizzled interacts with intracellular Disheveled
- Disheveled prevents the degradation of the beta-catenins by the destruction complex
- beta-catenins translocate to nucleus and activates transcription factors
Outline miRNA pathway.
- influence gene expression
- Dicer cleaves the miRNA precursor to make miRNA
- miRNA acts on AGO
- AGO-miRNA complex inhibits mRNA by cleaving it
