01-27: Signaling Pathways Flashcards
What are the 4 signaling factor families?
- transforming growth factor b
- fibroblast growth factor
- hedgehog
- Wnt
What are included in the transforming growth factor b family?
- TGF-b1»_space; TGF-b5
- Activin
- Inhibin
- Mullerian inhibiting substance
- Decapentaplegic
- Vg1
- BMP-1»_space; BMP-15
- Nodal
- Glial cell line-derived neurotrophic factor
- Lefty
What is TGF-b synthesized as?
a pair of inactive 390 amino acid precursors with a large proregion and a bioactive region
What is the large proregion of the TGF-b enzymatically cleaved from?
the bioactive region
How many proregion and bioactive regions are secreted from TGF-b?
2 proregions
2 bioactive regions
Which regions of TGF-b form a dimer?
the 2 bioactive regions
When is the TGF-b activated?
when proregions are separated from the bioactive dimer
What is the function of the bioactive dimer of TGF-b?
acts as a signaling molecule
What are the modes of action of bone morphogenic proteins (TGF-b family)?
- Inhibit other processes in the embryo
- Act by being inhibited by another molecule (in development of CNS)
- Bind to bioactive dimers and prevent them from binding to receptors
**Inhibit the inhibitors»_space; activates whatever the bone morphogenic proteins were inhibiting
What are 3 ways the fibroblast growth factor family regulate?
- Modification of interaction with heparan 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 the signal transduction machinery
What does the Hedgehog family relate to?
the segment polarity molecule in Drosophila
What 3 factors does the Hedgehog family include?
- Desert
- Indian
- Sonic hedgehog
What does the Wnt family relate to?
the segment polarity gene in Drosophila
What does the Wnt family often interact with?
components of extracellular matrix
What does the cytoplasmic domain of the receptors for fibroblast growth factors possess?
tyrosine kinase activity
What does the cytoplasmic domain of the receptors for TGF-b possess?
serine/threonine kinase activity
What are 6 signaling pathways?
- Delta-Notch pathway
- Receptor tyrosine kinase pathway
- Hedgehog pathway
- Wnt signaling pathway
- MicroRNA pathway
- Retinol pathway
What are the 2 components of the Delta-Notch pathway?
- On dominant cell = Delta (signal molecule)
- On neighboring cell = Notch receptor
What are the steps of the Delta-Notch pathway?
1- proteolytic cleavage of Notch intracellular domain
2- Notch intracellular domain complexes with Deltex
3- Complex enters nucleus (translocation)
4- Complex binds to Suppressor of Hairless
5- Notch-Deltex-Suppressor of Hairless complex binds to Enhancer of Split
6- Inhibitory signal represses gene expression
What is lateral inhibition?
a type of signaling between a dominant cell and a neighboring cell
neighboring cells will become something different than their environment
What is a dominant cell?
a cell in a population that begins to differentiate along a particular path
What uses the receptor tyrosine kinase pathway?
fibroblast growth factor signaling molecules
What are the steps of the Receptor Tyrosine Kinase pathway used by Fibroblast growth factor signaling molecules?
- FGF binds to receptor tyrosine kinase
- G protein = activated
- Activation of RAS, RAF, MAP kinase, ERK
- ERK translocated to nucleus
- Various transcription factors = activated
What are the steps of the Receptor Tyrosine Kinase pathway used by TGF-b?
- TGF-b binds to serine/threonine kinase receptor type II
- Receptor type II dimerizes with Receptor type I
- Activation and dimerization of R-Smad, Co-Smad
- Smad dimer translocates to the nucleus
- Binds to co-factors
- Co-factors bind to DNA regulatory factors
What are the steps of the Hedgehog pathway?
- Shh protein = complexed with cholesterol after being translated in sending cell
- Dispersed translocates Shh-cholesterol to cell surface
- Shh-cholesterol inhibits the inhibitory actions of Patched on Smoothened on the target cell (turns on Smoothened)
- Uninhibited Smoothened signals complex on microtubules to release the transcription factor Gli
- Gli translocates to the nucleus
- Gli influences gene expression
What are bound to an intracellular destruction complex within the target cell when there is no Wnt?
b-catenins
What are the steps of the Wnt signaling pathway?
- Wnt molecule binds to Frizzled on taget cell
- Frizzled interacts with intracellular Disheveled
- Disheveled prevents degradation of the b-catenins by the destruction complex (b-catenins now free)
- b-catenins translocated to nucleus
- b-catenins activate transcription factors
What are MiRNAs?
small non-coding RNAs that influence gene expression
What are the 2 major groups of MiRNAs?
- Piwi-interacting RNAs (piRNAs)
- Endogenous small interfering RNAs (endo-siRNAs)
When do piRNAs act?
during gametogenesis
When are endo-siRNAs expressed?
in somatic tissues throughout development
What are the steps of the microRNA pathway?
- Double helical miRNA precursor molecule cleaved by Dicer
- miRNA now active
- Complexed with AGO protein
- Complex approaches target mRNA
- Cleaves target mRNA molecule
- mRNA molecule now inactive
What are the steps of the Retinol pathway?
- Retinol (vitamin A) signal molecule binds to extracellular retinol-binding protein (RBP)
- Retinol RBP complex binds to membrane RBP
- Retinol released into cytoplasm
- Cytoplasmic retinol binds to CRBP1
- Enzymatic formations
- Retinoic acid bound to CRABP1 and translocated into nucleus
- Retinoic acid binds to dimer RXR-RAR
- RXR-RAR binds to RARE
- RARE activates transcription
