Membranes and Cell Signalling Coyler Flashcards
What is cross talk?
The influence of another pathway on a different one.
Where and by who was cycling AMP discovered?
1959 by Sutherland.
How is cyclic amp produced?
From ATP
What does cyclic amp do?
Acts primarily through a protein kinase. Stimulates glucose mobilisation for glycogen, fight or flight response, triglyceride breakdown.
Describe the production of cAMP?
Involves a receptor, a G-protein complex and the target/effector adenylate cyclase. When the ligand binds there is a conformational change allowing the G-protein to dock to the receptor. GDP is exchanged for GTP and the G-protein is activated and it’s three subunits fall apart. The alpha subunit moves independent of the beta and gamma subunits and performs work. The alpha subunit targets the effector and cAMP is produced from ATP.
What are second messengers?
Primary signal usually has a chemistry that cannot enter the cell therefore secondary messengers are required to convey the signal inside. Can be stimulatory or inhibitory.
What are PDE?
Phosphodiesterase, any enzyme that breaks a phosphodiester bond, 11 types.
How do PDE classes differ?
All have similar catalytic pore for the similar catalytic function and differ in regulatory and targeting features.
What does the work in the flight or fight response?
cAMP
What does cAMP do in the flight and fight response?
Changes the contraction from slow shortening and lengthening of contractile to a vigorous and rapid process. Drives phosphorylation in key sites to bring about profound changes in cardiac output and heart rate.
Why is control of fight or flight important?
To limit cAMP production to a short/small pulse
What do pathogens do to the flight or fight response?
They short circuit the control systems. Eg. Cholera toxin or bordettella pertusis
What are the control points of the fight or flight response?
Receptor is optimised for inactivity, receptor is internalised by the cell, G alpha hydrolyses GTP, GAP activates GTPase activity and therefore spreads the reaction to turn off the production of cAMP
Describe the catalytic enterty of cAMP-dependent protein kinase?
Small globular protein with 2 domains (N and C terminal), has specific constant between substrate and protein. Two subunits for catalytic activity and one for control or regulation.
What is the cAMP-dependent kinase deterred by?
Tyrosine at phosphorylation site: acidic residues at P-1, K at P+2 or F at P+4.
-3RRXSXXXX-4
Limited motif for the enzyme to read and activate on.
What is IP3?
Phosphoinositol 1,4,5 triphosphate
What are the roles of IP3?
Contraction in smooth muscles, fertilisation, aggregation of platelets (blood clots), secretion (cells of adrenal cortex).
Where does IP3 come from?
The internal leaflet of the plasma membrane, it’s substrate is a lipid with a inositol head group which is linked to a glycerol backbone as phosphatidylinositol
What are the two mechanisms of activation of phospholipase c?
Family of GPCRs which respond to light, acetylcholine and serotonin or platelet derived growth factor receptors
What’s the difference in the mechanism of regulation between GPCR activation of PLC and cAMP?
Both the alpha and beta gamma subunits have activity to activate PLC but only the alpha subunit activates cAMP
What is the mechanism of growth factor activation of phospholipase C?
Ligand binds to two platelet derived growth factors bringing the two kinase domains on the receptors close together which autophosphorylate one and other. Target residues are phosphotyrosine, SH2 domains recognise these. PlCgamma has a SH2 domain that is targeted to the PDGF.
What inhibits PLCgamma?
PKA can accces other sites on PLCgamma and phosphorylate to inactivate.
How can you destroy IP3?
Remove or add phosphate groups.
What is IP3 receptor?
The IP3 receptor, a calcium channel
