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G-protein mechanisms and PKA phosphorylation

What are G-protein coupled receptors? Integral membrane proteins
How are G-protein coupled receptors characterised? By 7 transmembrane-spanning helices within their structure
The activity of ion channels (include K+, Cl-, Ca2+ channels) is mediated by what? PKA-mediated phosphorylation
What allows modulation of transcription factors? Translocation of PKA into the nucleus
How is a beta-adrenergic receptor coupled to adenylyl cyclase activation? By the action of the alpha-subunit of the stimulatory G-protein called Gs
How is the original hormone signal amplified in trans-membrane signalling? Each molecule of bound hormone can stimulate many Gs-alpha-subunits
What effect does epinephrine have in muscle tissue? Converts glycogen to glucose
What do phosphodiesterases do? They terminate the cAMP signal
How do phosphodiesterases terminate the cAMP signal? By converting cAMP to its 5'-AMP metabolite
What is cAMP derived from? ATP
Which enzyme catalyses this conversion? Adenylyl cyclase
How is the activity of cAMP terminated? By the hydrolysis of cAMP to 5'-AMP by specific cAMP phosphodiesterases
How is adenylyl cyclase activation switched off? By the hydrolysis of GTP
As well as the adenylyl cyclase activation, what must also be switched off to return the cell to its resting, unstimulated state? The hormone-receptor complex
What are the three types of G-protein subunits? alpha, beta, gamma
Which subunit is specifically usually conferred by? alpha subunit, because it contains the GTP-binding site and an intrinsic GTPase activity
What are the 4 alpha subfamilies, and how have they been identified? Gs, Gi, Gq, and G12. Identified on the basis of their cDNA homology and function
How do G-protein coupled receptors bring about an intracellular response? They recruit guanine nucleotide-binding proteins (G-proteins) via their third cytoplasmic loop, to couple their signal transduction elements
What two groups can G-proteins be split into? Monomeric RAS-like G-proteins and heterotrimetric G-proteins
What second messenger are beta-adrenergic receptors coupled to? cAMP
Give an example of a beta-adrenergic hormone epinephrine
What does protein kinase A phosphorylate? Target proteins on serine and threonine residues
What subunits does PKA comprise of? Two regulatory subunits, and two catalytic subunits
How do ligands typically bind to G-protein coupled receptors? By sitting in a pocket formed by the 7 intracellular transmembrane-spanning alpha helices
What does ligation of a receptor initiate? A reaction with the GDP-bound heterotrimeric G-proteins
What does ligation of a receptor initiate? The exchange of GDP for GTP (including a change in G-alpha)
What do G-protein coupled receptors generally comprise of? -An extracellular N-terminus -Seven transmembrane-spanning alpha helices (20-28 hydrophobic amino acids each) -Three extracellular and intracellular loops -An intracellular C-terminal tail
What two families of transcription factors can be modulated by the translocation of PKA into the nucleus? cAMP-response-element-binding protein (CREB) and activation transcription factor (ATF)
What does the modulation of the transcription factors lead to? Either induction or repression of expression of specific genes
How do G-proteins exist at the inactive site? As heterotrimers with GDP bound to the alpha-subunit
How is downstream signalling activated by G-proteins? Activated G-alpha or G-beta subunits can interact with one or more effectors to induce intracellular secondary messengers, which activate downstream signalling
How is the G-protein anchored to the plasma membrane? By lipid modification of the gamma-subunits, and some of the alpha-subunits
Created by: SandersE