Question | Answer |
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 |