Intracellular Signalling 2 Flashcards
How do steroid hormones influence gene expression?
Steroid hormones are lipid-soluble so easily pass through the plasma membrane.
When the steroid hormone binds to its intracellular receptor, it undergoes a conformational change that allows the hormone-receptor complex to bind DNA.
The DNA-binding complex enters the nucleus and bind to specific gene sequences to influence gene expression.
What are the 3 major classes of membrane receptor?
Metabotropic
- G-protein coupled
Catalytic
- Tyrosine-kinase linked
Inotropic
- Ligand-gated ion channels
Describe the structure of GPCRs
7 Transmembrane alpha-helices
(Extracellular Amino terminus to Carboxyl intracellular terminus)
Ligand binding domain between loops 6&7
G-protin interaction domain between loops 5&6
What monomeric G protein is important in tyrosine kinase signalling?
Ras
True or False: The GDP-bound G-protein is the active form
False
The GTP-bound G-protein is the active form, which causes the G-alpha subunit to dissociate from the Gßgamma subunit.
Which G-protein subunit possesses GTPase activity?
The G-alpha subunit
How does adrenaline and glucagon stimulate glycogenolysis?
Activation of PKA (cAMP pathway) which inhibits glycogen synthase and activates glycogen phosphorylase kinase to activate glycogen phosphorylase to initiate the breakdown of glycogen.
How does adrenaline stimulate lipolysis?
Activation of PKA (cAMP pathway) which activates hormone sensitive lipase, which causes the breakdown of triglycerides into glycerol and free fatty acids.
Describe the pathway that inhibits adenylate cyclase.
Cannabinoid binds to CB1 receptor, activating Gi-protein. Gi-alpha subunit inhibits adenylate cyclase.
Give 3 examples of receptor tyrosine kinases.
Insulin receptor
Growth factor receptors
Cytokine receptors
True or False: Insulin has an inhibitory effect on apoptosis
True
True or False: Insulin has stimulatory and inhibitory effects on gene expression
True
Other than its effect on apoptosis in all cells, what is the other mitogenic action of Insulin?
Stimulation of DNA synthesis in all cells
Describe what happens when a ligand binds to a receptor tyrosine kinase?
Ligand binding induces receptor conformational change, which activates the receptor tyrosine kinase.
Autophosphorylation of one or more tyrosine in kinase domain
The autophosphorylation is associated with further kinase activation
Kinase phosphorylates tyrosine in non-catalytic regions of the receptor - these phosphorylated tyrosines act as docking sites for downstream signalling molecules to bind and become phosphorylated.
Describe the insulin signalling pathway and downstream effects of the signalling cascade to regulate blood glucose levels.
Insuline binds to RTK which undergoes a conformational change and autophosphorylation.
IRS1/2 binds to the phosphorylated tyrosine kinase and becomes phosphorylated.
PI3 kinase catalyses the conversion of PIP2 to PIP3, which activates Akt protein kinase.
Akt stimulates the insertion of GLUT4 transporters from the cytosol and into the plasma membrane to increase glucose uptake into the cell.
Akt also inhibits glycogen synthase kinase by phosphorylating the enzyme. Glycogen synthase is no longer inhibited by glycogen synthase kinase and can now convert Glucose-6-phosphate into Glycogen.
Akt can phosphorylate phosphodiesterase to convert cAMP back into AMP. This prevents PKA activation and thus prevents activation of hormone sensitive lipase and lipolysis.
