cell communication (lec 1-3) Flashcards
what are the three main things communication is needed for
development
homeostasis
breakdown
which type of signalling is like a whisper
contact dependant
which type of signalling requires an electrical connection
synaptic
which type of signalling uses gradients
paracrine
rank these in order of fastest to slowest
a)changing post translational modifications
b)changing structure of existing protein
c)changing protein via gene expression
b
a
c
why must target cells in endocrine signalling be specific
due to hormones being diluted in the bloodstream
which molecule is the precursor of most steroid hormones
cholesterol
what are the 2 classes of steroid hormones, give examples of each
corticosteroids(glucocorticoids and mineralocorticoids)
sex steroids(androgens, oestrogens, progesterones)
where are corticosteroids made
adrenal cortex
where are sex steroids made
gonads/placenta
what process occurs once the ligand has bound to a steroid hormone
translocation into the nucleus
act as transcription factors to regulate gene expression
what is the main type of receptor steroid hormones bind to
nuclear
what happens to primary response genes in secondary steroid signalling
they shut off
what is the process of cortisol being produced
CRH in hypothalamus
ACTH in pituitary
adrenal gland releases
what is cortisol
a glucocorticoid steroid hormone released in response to stress
what happens with primary adrenal sufficiency of cortisol
damage to the adrenal glands
what happens with secondary adrenal sufficiency of cortisol
lack of ACTH
how do you distinguish between primary and secondary adrenal sufficiency
give a shot of ACTH and if the person responds, they have secondary
what are the causes and symptoms of addisons disease
too little cortisol
depression, nausea, weight loss
what are the causes and symptoms of cushings disease
too much cortisol
weight gain, raised BP
what is the process of insulin signalling
insulin binds to receptor(a RTK)
tyrosine phosphorylation of insulin receptor substates and proteins
binding of PI3K to p tyrosine sites, which synthesises PIP3
PIP3 recruits PDK, which directly phosphorylates AKT
AKT then Phosphorylates other substrates to ensure glycogen synthesis and glucose uptake
how does metformin treat type 2 diabetes
activates AMPK
which part of a TRK is hydrophilic
cyteine domain
which part of a TRK interacts with downstream signalling machinery
tyrosine kinase domain
what are the 2 different ways of transmitting info across a membrane
conformational change
dimerisation/multimerisation of transmembrane receptors
which disease is associated with long term steroid abuse
cushings
describe the phosphorylation of the insulin receptor
conformational change moves the 2 kinase domains closer together
kinase domains trans-phosphorylate
in addition, a closely associated docking protein insulin receptor substrate also becomes phosphorylated
what is the main difference between intracellular receptors and cell surface receptors
intracellular are within cells
cell surface are on the cell surface
which conserved elements does the hydrophilic domains of a TRK contain
Ig s
EGFs
describe the transmembrane region of a RTK
20-25 aa of alpha helical structure
stabilised via interaction with fatty acid chains
describe the RAS/RAF/MEK/ERK pathway
growth factors PDGF bind to RTKs on cell surface and cause phosphorylation(elbows)
the RTKs serve as docking sites for adapter proteins (grb2)
Grb2, via its SH2 and SH3 domains, recruits a type of GEF called SOS
SOS swaps GDP of GTP which activates Ras
Ras binds to inhibition domain of Raf which then activates itself
MEK is then activated which in turn activates ERK
pErk translocates into nucleus and triggers gene expression
how is the Ras pathway regulated
by negative regulation
how is Raf negatively regulated
by its own n terminal region
phosphorylation activates it
how does Erk contribute to negative regulation
contributes to negative phosphorylation of Sos so prevent its binding to Grb2
describe the location, activation and regulation of small GTPases
membrane tethered
activated by being bound to the GTP nucleotide
regulated by GEFs and GAPs
what is the main function of the Ras family
relay signals from RTKs
what is the main function of the Rho family
relay signals from surface receptors to cytoskeleton
what do mutations in the Ras/Raf/MEK/ERK mainly cause
melanomas
How can you treat melanomas
use bRAF and MEK inhibitors
what is the purpose of the JAK/STAT signalling pathway
immune system regulation
What is a receptor associated tyrosine kinase
a receptor that itself doesnt have intrinsic phosphorylation properties
describe the JAK/STAT singaling pathway
cytokines bind to RTKs/receptors associated with JAK kinases
dimerisation occurs which brings JAKs into proximity
STAT proteins doc to JAKs which leads to phosphorylation of specific tyrosine residues
what is JAK and how many are present
a kinase
4
what is STAT and how many are present
a signal transducer and activator of transcription
7
What does the TPO pathway result in
platelet formation
what does the EPO pathway result in
erythrocyte production(rbcs)
what does mutant JAK2 cause
fibrosis in bone muscle
how can fibrosis in bone marrow be treated
ruxolitinibs( a JAK2 inhibitor)
where is Ras located
on the inner side of the plasma membrane
