Lecture 7: signaling pathways Flashcards
What are the 4 signaling factor families?
- Transforming growth factor-Beta Superfamily
- fibroblast growth factor family
- Hedgehog family
- Wnt family
Describe TGF-B1
disulfide linked dimer
starts out as a pro region and a bioactive region; these two pieces are cleaved and the two sections are secreted. then the bioactive regions form a dimer, and then reform, and separate to leave a bioactive dimer that is able to act as a signaling molecule
What is the overall function of the transforming growth factor beta superfamily?
bone morphogenic proteins that are able to inhibit other processes in the embryo
Describe the fibroblast factor family
22 members that are able to modify interaction with the heparin proteoglycans in the receptor complex; regulation at the membrane
Describe the hedgehog pathway
related to the segment polarity molecule: include desert, indian, and hedgehog
Describe the Wnt family
related to the polarity gene segment in the fly and interacts with the extracellular matrix
What are examples of signaling pathways?
- delta notch
- receptor tyrosine kinase pathway
- hedgehog pathway
- Wnt signaling pathway
- microRNA pathway
- retinol pathway
Describe the delta notch pathway
The dominant cell has the delta signal and then neighboring cell has the notch receptor; they bind and then the intracellular domain of notch binds to DEltex which goes into the nucleus to the suppressor of hairless and binds to enhancer of split which represses gene expression
Describe lateral inhibition
A dominant cell expresses the delta receptor which then travels to the neighboring cells and causes transcription repression which allows the delta to remain the dominant cell
Describe the receptor tyrosine kinase pathway (by fibroblast growth factor)
- FGF binds to RTK
- G protein activation
- RAS
- RAF
- Map kinase
- ERK
- phosphorylation of transcription factors
Describe the receptor kinase pathway (by transforming growth factor-beta signaling)
- TgF-B binds to serine/threonine kinase receptor type II
- receptors I and II dimerization
- Rsmad and Co-Smad dimerize
- Smad goes to the nucleus and binds to the DNA regulatory factors
Describe the hedgehog pathway
- sonic hedgehog protein is complexed with cholesterol after being translated in the sending cell
- Shh-cholesterol is translated to the cell surface via Dispersed
- shh cholesterol inhibits Patched on Smoothened in the target cell
- Uninhibited smoothened signals release transcription Gli from a complex on micritubules
- Gli translocates to the nucleus and increases gene expression
Describe the Wnt signaling pathway
When Wnt is absent, the beta catenins are bound to intracellular destruction complex within the target cell
- Wnt binds to Frizzled on target cell
- Frizzled interacts with intracellular Disheveled
- disheveled protects the beta catenins
- these catenins translocates to the nucleus and activates transcription factors
Describe the microRNA pathway
- miRNA precursor is cleaved by Dicer
- miRNA is loaded with AGO and forms a complex
- this complex goes and cleaves the target mRNA
What are the two groups of miRNA
- piwi-interacting miRNA(during gametogenesis) and ends-siRNAs (somatic tissues through development)
Describe the retinol pathway
- retinol binds to the extracellular retinol binding protein (RBP)
- retinol RBp complex binds tot he membrane RBP
- retinol is released into the cytoplasm and binds to CRBP1
- series of enzymatic transformations, retinoic acid binds to CRABP1 and translocation in the nucleus
- retinoic acid binds to the dimer RXR-RAR which binds to RARE and activates transcription
