Biosignaling Flashcards
What is signal transduction?
Non covalent interaction a ligand and a receptor
4 major features of signal transduction
Specificity; Amplification; Desensitization/adaptation; Integration
Features of specificity (4)
Complementarity; non-covalent bond (so it can end); tissue-specific receptor/receptor target
Do every cells express receptors?
No
Can differentiated cells can have similar receptors?
Yes, but may respond differently: it explains why a single hormone can affect many cells
Explain specificity of TRH
Thyrotrophin releasing-hormone is secreted from hypothalamus to control expression of thyroid gland and TSH, but it has no effect on hepatocytes (lack of receptor)
Explain specificity of adrenalin
Affects glycogen metabolism in hepatocytes, but not adipocytes (receptors in both, but the last ones can’t express a response)
Amplification is responsible for…
Enzyme cascade of action (it explains relative speed of action)
What is desensitization/adaptation of signal transduction?
No more response to an actual signal.
Eg.: Smell, bright to dark light, skin sensation of clothes
Integration is a feature of signal transduction…
Ultimate response depends on what type of signal are coming in (somation)
Some signals to which cells respond…
Antigens, glycoproteins, oligosaccharides, xtracellular matrix components, growth factors, hormones, light, mechanical touch, neurotransmitters, nutrients, odorants, pheromones, tastants
A ligand-receptor interaction can have a direct response (inducing a change) or…
Further levels of interaction inducing activity of effectors which then respond
There are six major types of receptors…
G-protein coupled; tyrosine kinase; guanylyl cyclase; ashesion (integrin); gated ion channel; nuclear
What is the special class of receptor?
Nuclear ones (in the nucleus)
G protein-coupled in short
External ligand binds to receptor; it activates an intracellular GTP-binding protein, which regulates an enzyme that generates a second messenger (the actual response)
Example of G-protein receptor?
Epinephrine
First step of G prot
1- Substrate-receptor interaction (non-covalent)
2nd step G prot
2- GDP-Gs become GTP-Gs activated (phosphorylated by GTP)
3rd step G prot
3- GTP-Gs activated moves to adenylyl cyclase and activates it
4th step G prot
Adenylyl cyclase catalyzes the formation of cyclic AMP
5th step of G prot
cAMP activates PKA (protein kinase A)
6th step of G prot
PKA phosphorylates other proteins, producing a response
7th step of G prot
cAMP is degraded, no longer activation of PKA
What is the enzyme activated in the G prot example of epinephrine?
Adenylyl cyclase
What is the second messenger regulated by the enzyme in G prot example of epinephrine?
cAMP
How does the second messenger induces a response to epinephrine?
cAMP activates PKA, which phosphorylates concerned cell components
What is the actual G prot?
GDP-Gs + y and B subunits. It desactivates itself with intrinsic GTPase activity (when activated)
When is the GDP-Gs prot is bound to B and y subunits?
When inactivated
What is the precursor of second messenger?
ATP
What is the enzyme activating the second messenger?
Adenylyl cyclase
Anatomy of PKA
Core: AKAP, 2x C (catalytic) and R (regulatory) subunits
What is the conformation of PKA when inactive; when active?
Inactive = C bound to R Activated = C (also substrate-binding cleft) free and R are facing the opposite
What is activating PKA?
4 cAMP that bind to R subunits, switching their conformation
cAMP is acting on which specific aa (3)?
Serine and threonine, + tyrosine
3 enzymes regulated by cAMP-PKA?
Glycogen synthase; phosphorylase kinase b; pyruvate kinase
Other G-coupled receptors example?
Ghrelin; gonadopropin; thyrotropin hormone; prostaglandins
How does signal amplication work, and to which fold?
Enzyme cascade; 10 000 folds
There are two possible ends for G-coupled signals
cAMP cut into AMP; intrinsic GTPase activity (GAP, GTPase activator protein, and RGS, regulator of g-protein signaling)
What are the role of GTP-GDP exchange factors?
To stimulate activation of GTP-Gs activated by GTP
What are the GTP-GDP exchange factors?
rh: rhodopsin; Sos: Son of Seven
Signal desensitization in G-prot: step 1
Epinephrine binds to its receptor and activates GTP-Gs activated
Signal desensitization in G-prot: step 2
GsBy (subunit left behind) recrutes bARK (b-adrenergic receptor kinase) to the membrane, which phosphorylates the receptor
How does bARK phosphorylates the receptor?
Ser residues of its carboxyl end
How many phosphorous groups added from bARK?
2
Signal desensitization in G-prot: step 3
B-Arrestin (B-Arr) binds to the phosphate groups (carboxyl terminal of the receptor)