[FMS] CBS - intracellular signalling Flashcards
which one of these is NOT an example of an extracellular signal for amino acids and derivatives:
glutamate,
estrogen
adrenaline, dopamine
oestrogen
which one of these is NOT an example of an extracellular signal for a steroid:
glutamate,
oestradiol, testosterone
cortisol, aldosterone
glutamate
give an example of an extracellular signal released by prostaglandins
eicosanoids - derived from arachidonic acid
which one of these is NOT an example of an extracellular signal for proteins and peptides
insulin,
glucagon,
growth factor
aldosterone
aldosterone
which one of these is NOT an example of an extracellular signal for gases
nitric oxide, carbon monoxide
carbon dioxide
carbon dioxide
what are the 5 different ways cells can signal to eachother
endocrine
autocrine
paracine
contact dependent
neuronal
definition of endocrine signals
signal produced by cells in one part of body, travels in blood to target other cells
definition of autocrine signals
signal acts on same cell that produces it
definition of paracrine signals
signal produced by cell and acts on other cells that are very close
definition of contact dependent signals
signal is integral part of one cell and interacts directly with another cell
definition of neuronal signals
electrical signal transmitted down cell and message passed to another via synapse (neurotransmitter)
signals can bind to different receptors, what 2 receptors can adrenaline bind to?
β adrenergic receptor (adrenaline)
α adrenergic receptor (adrenaline)
whats the nature of a cell surface receptor? hydrophilic or hydrophobic?
hydrophilic
whats the nature of an intracellular receptor? hydrophilic or hydrophobic?
hydrophobic
give an example of a hydrophilic cell surface receptor (hormone)
adrenaline
give an example of a hydrophobic intracellular receptor (hormone)
steroid hormones
difference between how hydrophilic and hydrophobic hormones interact?
hydrophilic = doesn’t enter
hydrophobic = enters cell
- Cell surface receptor
– Hormone is hydrophilic e.g. adrenaline
– Binding of hormone triggers response inside cell
– Hormone does not “enter” the cell - Intracellular receptor
– Hormone is hydrophobic e.g. steroid hormones
– Hormone crosses the plasma membrane
– Hormone binds to receptor in the cytosol and triggers a response
inside cell
there are different types of signalling, give an example of what binds to a signal receptor when the depolarisation of membrane due to flow of ions occurs
acetylcholine
there are different types of signalling, give an example of what binds to a signal receptor when the direct activation of transcription factor occurs
steroid
there are different types of signalling, give an example of what binds to a signal receptor when the generation of secondary message inside cell occurs
glucagon – cAMP
there are different types of signalling, give an example of what binds to a signal receptor when the Direct activation of enzymatic kinase cascade occurs
EGF – MAP kinase pathway
ion channels like acetylcholine bind to …… …… receptors
nicotinic acetylcholine receptor
3 examples of ions that go through the ion channels in a nicotinic
acetylcholine receptor
Na+, K+, Ca2+
How does the direct activation of transcription factors occur?
- Steroid hormones contain a hormone binding domain, a DNA binding domain and a domain for interacting with other transcription factors
- Binding of steroid induces conformational change that allows DNA binding and activation of transcription of target genes
- Sequence specific DNA binding domain – hormone response elements in sequence of target genes
- They are ligand–dependent transcription factors
Which of these is not a secondary messenger
cyclic amp
ip3/DAG
Ca2+
Na2+
nitric oxide
cyclic GMP
Na2+
what are secondary messengers generated by?
enzymes
what can GPCR activate?
- adenylyl cyclase (adenylate cyclase)
- phospholipase C
what does adenylyl cyclase produce?
adenosine 3’:5’ - cyclic monophosphate (cAMP)
what 2 things does phospholipase C produce?
inositol 1,4,5-trisphosphate (IP3)
1,2-diacylglycerol (DAG)
how many transmembrane domains does GPCR have?
7
how many transmembrane helices are there in GPCR and are they alpha or beta?
7, transmembrane ALPHA helixes
what kind of complex is Guanine nucleotide binding proteins (g-proteins)
heterotrimeric - made up of alpha, beta, gamma subunits
where is the g-protein interaction domain on GPCR, the exterior or the cytosol?
cytosol
where is the n-terminal and c-terminal located in GPCR
n terminal (NH3) B
on exterior
c terminal (COO-) in cytosol
what happens when GTP binds to a g-protein
dissociates when GTP binds
in what form is a g-protein active, and in what form is it inactive?
active = when GTP binds to alpha, and this dissociates from β and γ
inactive = when GTP is hydrolysed to GDP, therefore alpha reassociates back to β and γ
outline what happens in the interaction between GPCR with G-proteins to make effector enzymes
what does cAMP activate?
protein kinase a - PKA
what kind of enzyme is pKA? what subunits is this enzyme composed of?
tetrameric enzyme - 2 regulatory (R) and 2 catalytic subunits (C)
when pKA is inactive what state does it exist in? and how is it activated.
it exists as a tetramer when inactive, when cAMP binds to the R sub units it activates the C sub units
how do you get from phosphorylase kinase b to phosphorylase kinase a
how do you get from phosphorylase b to phosphorylase a
how do you get from glycogen to glucose-1-phosphate?
how do you get from glycogen synthase a to glycogen synthase b
ATP + adenylyl cyclase =
cAMP
cAMP + phosphodiesterase =
AMP
what does PKA phosphorylate and why?
- PKA phosphorylates CREB (cAMP response element binding protein)
- CREB binds to specific sequences in target genes stimulating transcription
^ long term adaptation to starvation: changes in gene expression
Some GPCR contain Gαq (Gq) subunit, what does dissociated Gq do?
Dissociated Gq activates phospholipase C
which 2 inositol phospholipids does phospholipase c cleave in the membrane?
Diacylglycerol (DAG)
Inositol 1, 4, 5 trisphosphate (IP3)
what channel does IP3 activate in the endoplasmic reticulum and what happens as a result?
IP3 activates Ca2+ channel in endoplasmic reticulum
as a result, Ca2+ concentration increases in cytosol
what 2 things activate phospholipase c?
DAG together with Ca2+
what binds to tyrosine residues in cytoplasmic domain of receptor (RTK)?
EGF
What happens when EGF binds its specific receptor?
The EGF receptor dimerizes and triggers the autophosphorylation of tyrosine residues in
cytoplasmic domain of receptor : Receptor Tyrosine Kinase (RTK)
Adaptor proteins contain phosphotyrosine binding domains, what are the 2 binding domains?
– SH2 (src – homology 2)
– PTB (phosphotyrosine binding)
what adaptor proteins must bind to the receptor to activate the exchange of GDP-Ras → GTP-Ras
GRB2 and SOS
what is the structure of Ras?
Ras is monomeric G-protein
what does GTP-Ras trigger?
a kinase cascade
outline Ras-MAP kinase pathway
just remember Ras - 3 - kinases (starts with KKK and then goes KK, then K)
is Ras-MAP kinase pathway a secondary messenger?
no - because the signal is amplified, not transmitted from one thing to another
difference between a primary and secondary messenger?
Primary Messenger: The signaling molecule (such as a hormone or neurotransmitter) that binds to a receptor on the cell surface, initiating the signaling process.
Secondary Messenger: Small molecules inside the cell (like cAMP, Ca2+, inositol trisphosphate - IP3, diacylglycerol - DAG, etc.) that are generated or activated in response to the binding of the primary messenger to the receptor.
what is convergence?
Different signals trigger different pathways but cause the same effect in the cell
what is cross talk?
different signals trigger different pathways blocking each other
for example - EGF signalling via phosphotyrosine kinase and Ras-MAP kinase but adrenaline inhibiting one of the steps via PKA action
do quiz on keats and write down what score i got
https://keats.kcl.ac.uk/mod/quiz/view.php?id=7540217
whats the structure of a G-protein
- Heterotrimeric complex
which enzyme activity does the second messenger DAG activate?
adenyl cyclase
phospholipase C
protein kinase A
protein kinase C
tyrosine kinase
Protein Kinase C
