TK and nuclear hormone receptors Flashcards
Tyrosine kinase has a double extracellular region (N terminal). True or false?
False - single extracellular region
The extracellular region includes binding site for ____________
chemical messenger
It has a single hydrophobic region that traverses the membrane as an alpha helix of ____ turns
7
The C-terminal chain is inside the cell membrane and acts as a _________
catalytic binding site
TK receptors have a dual role. They act as _______ and _______
enzymes
receptors
In the resting state, does the receptor have any catalytic activity?
No - the active site is hidden
What happens when the ligand binds to the receptor?
The receptor changes shape and reveals the active site on the C-terminal chain - phosphorylation can now occur
What is required to supply the phosphate?
ATP
EGF is a bivalent ligand. What is meant by this?
It can bind two receptors at the same time
What happens when EGF binds receptors?
Results in receptor dimerisation and activation of enzyme activity
Phosphorylation can take place even if dimerisation doesn’t occur. True or false?
False
Some insulin receptors already exists as dimers or trimers and only require the binding of a ligand. True or false?
False - exists as dimers or tetramers
The insulin receptor is a homotetrameric complex which acts as a TK receptor, True or false?
False - heterotetrameric
What is the difference between TK receptors and TK linked receptors?
TK linked receptors require an extra step because they do not have catalytic activity in their C terminal chain. Ligands can bind and dimerise and then activate a TK enzyme from the cytoplasm (extra step)
Once the kinase receptor has been phosphorylated, the phospho-tyrosine groups acts as binding sites for ____________
signalling proteins
signalling proteins cannot become phosphorylated. True or false?
False - they can become phosphorylated and act as further binding sites
What determines the type of signalling that takes place?
The protein that has managed to bind to the kinase receptors
Some growth factors activate _________ leading to calcium release
phospholipase C
Some TK receptors can catalyse the formation of ____ from GTP
cGMP
cGMP opens _______ channels in the kidney which promote the excretion of _______
sodium
sodium
TK receptors are more important than GPC receptors. True or false?
False - second most important drug targets after GPC
Which human diseases is kinase activity implicated?
Cancer
Rheumatoid arthiritis
Asthma
Psoriasis
How can modulation of kinase activity be achieved?
Inhibition of phosphorylation activity by blocking ATP binding
Disruption of protein-protein interactions
Down-regulation of kinase gene expression
Which drug inhibits abnormal kinase in chronic myeloid leukaemia?
Imatinib mesylate
Which two drugs target ATP binding to EGFR (which is overexpressed in tumours)?
Gefitinib
Erlotinib
Which two drugs block the receptor protein kinase?
Cetuximab
Panitumumab
Which drug blocks a ligand from binding to receptors?
Bevacizunam
