Strand 3 - Cell signalling Flashcards
what is the first stage of signal transduction? (hint: involves the first messenger)
an extracellular signal molecule activates a membrane receptor
what is the second stage of signal transduction
intracellular molecules are transduced via a certain pathway
what is the third stage of signal transduction?
activating a cellular response
give an example of an amine which is a first messenger
adrenaline
give an example of a peptide/protein that is a first messenger
angiotensin 2
insulin
give an example of a ligand gated ion channel (hint: think nervous system)
nicotinic ach receptor
which subunits make up the nicotinic ach receptor
2 alpha
1 beta
1 delta
1 epsilon
which ion is GABA A selective for?
Cl-
which two substances activate GABA A receptors?
alcohol and anaesthetics
name a muscarinic receptor which activates a potassium channel
GABA B
what are metabotropic receptors connected to? and what does it do?
connected to a G protein
opens ion channels
what do ionotropic receptors form in the membrane? what does this allow?
a pore
allows an ion to pass into a cell
how many chains are G proteins made of? what are they?
3
alpha, beta, gamma
the alpha subunit of a G protein has a …… binding site that binds…….
guanine
GTP/GDP
does alpha GDP have a high affinity for the resting B-gamma or the active one?
resting
the alpha subunit of a G protein hydrolyses GTP. what molecule does this activate?
adenyl cyclase
in an inactive PKA molecule are the subunits bound together or not?
does the R subunit suppress the activity of the C subunit
yes and yes
the R subunits in PKA have how many binding sites for cAMP?
2
which 2 chains does PKA have?
catalytic and regulatory
What does PKA catalyse the transfer of to serine or threonines on substrates?
ATP
which cellular response is activated by cAMP in the kidney collecting duct?
water retention (vasopressin)
which cellular response is activated by cAMP in the smooth/cardiac muscle?
relaxation of muscle / increase of heart rate (adrenaline)
which cellular response is activated by cAMP in the colonic epithelium?
promotion of fluid/electrolyte secretion
which cellular response is activated by cAMP in the pancreas?
promotion of the release of glucose in the blood (glucagon)
what is cAMP hydrolysed by?
phosphodiesterase
phosphodiesterases are inhibited by which substance?
caffeine
what does Beta adrenoreceptor kinase do to a beta adrenoreceptor?
what effect does this have on the affinity it has for adrenaline?
phosphorylates it
reduces affinity for adrenaline
what does the stimulatory alpha subnit stimulate in a G protein?
adenyl cyclase
what does the inhibitory alpha subnit inhibit in a G protein?
adenyl cyclase
which alpha subunit of a G protein does the cholera toxin act on?
the alpha stimulatory subunit
when cholera toxin binds to the alpha stimulatory subunit of a G protein what does it cause to happen to ADP?
what does this cause to happen to the alpha subunit in turn?
ADP ribosylation
hydrolysis of GTP = constant activation of alpha subunit
in the colon, the cholera toxin activates what?
what does this cause in turn to be excreted from the body?
PKA dependent Cl- channels
secretory diarhhoea
which alpha subunit of a G protein does pertussis toxin act on? and what does it prevent?
what does this increase therefore ?
the inhibitory alpha subunit - prevents activation by receptors and increases cAMP
what does pertussis toxin lead to in the airways?
whooping cough
which unique subunit do Gq proteins contain?
alpha q-11
what do Gq proteins allow hormones to do?
activate the amplifier enzyme phospholipase C
What does phospholipase C cleave to produce IP3 and DAG?
PIP 2
what does IP3 stimulate the release of from the ER?
Calcium
what does DAG recruit when it remains in the membrane?
Protein kinase C
how many Ca2+ does each calmodulin bind to ?
4
what doe the Ca2+/CaM complex activate?
CaM kinases
What do CaM kinases cause the contraction of in the body?
smooth muscle
which 2 residues do CaM kinases phosphorylate?
serine and threonine
What can PKCs potentiate the effect of which in turn mediates the desensitization via cf Beta- ARK?
IP3
What does alpha 1 adrenoreceptor cause the constriction of?
vascular smooth muscle
Which G protein causes blood pressure to increase?
Gq-PLC-IP3-CaMK
Which G protein causes blood pressure to decrease via vasodilation?
Gs-cAMP-PKA
which 3 subtypes (out of 1-5) of muscarinic receptors are Gq coupled stimulatory?
1, 3, 5
**which 2 subtypes (out of 1 to 5) of muscarinic receptors are Gi protein coupled inhibitory?
2 and 4
which 2 receptors are coupled with a Gi protein? (hint: one adrenergic and one muscarinic)
a2 adrenergic
M2 muscarinic
what is the function of the guanyl cyclase domains on guanyl cyclase receptors?
to convert GTP to cGMP
give an example of a response from an activated guanyl cyclase receptor?
vasodilation/ relaxation of vascular smooth muscle
what is the function of the Ser-Thr domains on Ser-Thr kinase receptors?
phosphorylation of target proteins
give an example of a response elicited by an activated ser-thr kinase receptor?
cell proliferation
what 2 things do tyrosine kinase domains in TKRs phosphorylate?
themselves and other proteins
give an example of a response caused by an activated tyrosine kinase receptor?
insulin mediated glucose uptake / storage in liver or muscles
tyrosine kinase associated receptors do not contain which type of domain?
kinase domains
what does the dimerization of tyrosine kinase associated receptors cause the activation of? Give an example
associated tyr kinases such as JAK2
give an example of a cellular response elicited by the activation of a tyrosine kinase associated response
EPO mediated increased production of blood cells
what do the tyrosine phosphatase domains dephosphorylate in tyrosine phosphatase receptors?
target proteins
give an example of a response elicited by the dephosphorylation of target proteins by tyrosine phosphatases
maturation of lymphocytes
what is glucose stored as in the liver and muscles?
glycogen
after a meal what happens to glucose absorption?
increases