FOM 6.5.2 Flashcards
What is signal transduction?
Process by which environmental cues (signals) are detected and communicated (transduced) throughout the cell to elicit a specific cellular response
What are some common themes in signal transduction?
conformational changes of proteins, post-tln modification of proteins, protein translocation, protein-protein interaction, generation of 2nd messengers, altered gene txn, down-reg
What does GPCR stand for?
G-protein coupled receptor
What are the basic characteristics associated with G protein coupled receptors?
7 transmembrane domains, receptor for many ligands, target of many drugs, and binds and activates heterotrimeric G-proteins
What are the basic characteristics of the G-proteins?
These are a heterotrimeric protein complex (alpha, beta, and gamma). The alpha subunit is bound to GDP
What is the basic signalling pathway through the GPCR?
Binding of the ligand induces a conformational change of the receptor which causes a conformational change on the heterotrimer proteins. GDP on the alpha subunit is replaced by GTP on the alpha subunit which leads to activation. The heterotrimeric proteins will dissociate and go effect their target molecules by binding to them.
Why do effector molecules interact with the heterotrimeric proteins only after the alpha subunit has bound GTP?
The interface between the alpha and beta-gamma subunit is very tight which creates a shield against any effector molecule.
What role does specificity have in GPCRs?
There are 4 different families and many other subfamilies of each sub-unit. Diverse combinations lead to different responses. Different G-protein isoforms. Binding multiple ligands with different affinities. Varied responses given ligand concentration.
What is the process of desensitization of the G-protein and what is the end result?
Intrinsic GTPase cleaves GTP yielding GDP. However, this is a slow process and is aided by RGS which can increase the rate of this by 2000 times. The beta and gamma sub-units then re-associate with alpha and can no longer affect downstream molecules.
What is the process of heterologous desensitization of the GPC receptor?
PKA and PKC will phosphorylate ligand-occupied and ligand-unoccupied GPCRs. After this the receptor will not be able to interact with the heterotrimer proteins. This will also decrease the affinity of the receptor to the ligand.
What is the process of homologous desensitization of the GPC receptor?
The protein GRK will phosphorylate only ligand bound GPCRs which will recruit and bind arrestins. The phosphorylated and arrestin bound GPCRs cannot interact with the heterotrimer. Arrestin-bound GPCR is internalized and either dephosphorylated or degraded.
What are the roles of beta-blockers in GPCRs?
Beta-blockers bind to and block the GPCR that epinephrine and norepinephrine would normally bind to. This would lead to decrease cardiac output and decreased BP.
What effect does cholera have on GPCRs?
The toxin produced by cholera doesn’t allow for hydrolysis of GTP so the signal is constantly active.
What effect does the pertussis toxin have of GPCRs?
This toxin leads to G-protein heterotrimer not binding to the receptor, and the cell not able to elicit a response to stimuli. This leads to the inability of the cell to carry out normal processes.
What is Jansen’s metaphysical chondrodysplasia and its effect on GPCRs?
This is from ligand-independent G-protein activation. This signaling complex believes it is always on even when not in the presence of any signal. This results in hypercalcemia from increased bone reabsorption because the cells are responding to PTH signaling that doesn’t exist.
