Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
19 Cards in this Set
- Front
- Back
|
How do members of the type II receptor tyrosine kinase (RTK) family function? |
- as heterotetramers - 2 ligand binding alpha subunits - 2 beta subunits containing TK activity |
|
|
How is plasma glucose controlled? |
- glucose-decreasing action of insulin - glucose-increasing action of anti-insulin hormones |
|
|
What is an activation loop? |
- most kinases possess it - blocks target binding site of the kinase - requires phosphorylation to be moved out of the way |
|
|
What are Cam loops? |
- Cam loops form where the a-subunits join the b-subunits - found in the insulin receptor |
|
|
How do Cam-loops work and why are they important for InsR function? |
- in absence of ligand - keep a-subunits apart, which forces b-subunits apart - the receptor is inactive - i presence of ligand - cam loops rotate and allow a-subunits to close around 1 ligand, which causes b-subunits to move together - TK can now phosphorylate target tyrosines on b-subunit of opposite receptor (cross-phosphorylation) |
|
|
Signalling via the InsR (image) |
|
|
|
How is glucose uptake in muscle and fat cells regulated? |
- Glucose transporters are stored in walls of cytoplasmic vesicles - Insulin induced IRS-1/PI3 kinase/Akt signalling triggers vesicle translocation to the plasma membrane - vesicles fuse with membrane where they take up glucose and pass in to the cell |
|
|
How is the production of insulin-like growth factors (IGFs) regulated? |
- by growth hormones (GHs) - majority are produced in the liver (feedback inhibition for GH and some endocrine action) - the remainder of IGFs is produced in peripheral tissues (regulates skeletal and tissue growth, cellular differentiation) - GH levels are regulated by many factors (stress exercise, nutrient levels and sleep) |
|
|
What are the differences between IGF-1 and insulin (4)? |
- IGF-1 does not have receptors in liver and fat - GH is the main stimulator of IGF but causes only minimal insulin release - IGF has feedback inhibition of GH secretion while insulin has no effect on GH - IGF regulates growth and differentiation, while insulin regulates glucose metabolism |
|
|
Components of the IGF-1R signalling system? |
- Ligands - IGF-I and IGF- II (produced in liver or locally by cell itself) - IGF-binding proteins - IGFBP proteases - act on IGFBP to release ligand - Receptors |
|
|
How are IGF-1 and insulin synthesis and secretion regulated? |
- co-ordinately (due to their ancestral linkage) by changes in nutrient levels - IGF-1 can stimulate glucose uptake in skeletal muscle - Decrease in calories/food = reduced IGF-1 levels, reduce in GH, limited growth. |
|
|
How do Ins/IGF work in C.elegans and D. melanogaster (receptor)? |
- they share a receptor -orthologue of mammalian insulin and IGF-1 receptors - key components of the pathway are highly conserved |
|
|
What is the result of having a common receptor for IGF and insulin? What happens if Ins/IGF signalling is lacking? |
- metabolism and growth are tightly linked with nutrient supply - in larva - lack of Ins/IGF - dormant state in times of nutrient deprivation (dauer formation) - in adult - inhibited reproduction and increased lifespan |
|
|
What are ILPs? |
- Insulin-like peptides - bind DAF2, which works as heterotetramers (similar to InsR) - ILPs show the greatest homology to human insulin |
|
|
What happens when DAF2 is activated by ILPs? |
- Akt is activated - it phosphorylates DAF 16, which forces it to remain in the cytoplasm instead of entering nucleus - DAF16 regulates growth and development |
|
|
What happens if DAF 2 is not activated? |
- No akt => DAF16 is unphosphorylated - enters nucleus to drive transcription - genes regulating stress responses are induced dauer formation/inhibition of reproduction |
|
|
Experiment with C. elegans - the role of DAF2: |
- control - lives 30 days - reduced DAF2 - slightly increased longevity (50 days) - negligible DAF2 - RNAi = even more increased longevity (90 days) - negligible DAF2 - RNAi + gonad removal = 170 days (similar results in Drosophila) |
|
|
Is there a role in Ins/IGF-1 signalling in influencing ageing in mammals? |
- IGF-1R knockout , or mutations or low GH and IGF (snell mouse) = increased lifespan |
|
|
Give example in Ins/IGF-1 involvement in ageing in humans? |
- Ashkenazi Jewish people - IGF-1R polymorphisms -linked with longevity in centenarians |
