signal transduction

receptors

molecules within or on surface of target cells to which substance endogenous to organism attaches itself with high affinity and specificity

signal transduction

process by which cell responds to subs outside cell through signalling molecules found on surface of or inside cell

endogenous

produced from within body - internal cause or origin

role of receptors

generate amplification cascades and integrate multiple signals to produce regulatory outcomes

receptors exhibit…

specificity

receptor desensitisation refers to

decrease in response of a receptor to a molecule eg. drug resulting in reduced effect

amplification cascade

enzymes activate other enzymes amplifying effect of initial stimulus

integration

regulatory outcome of 2 signals with opposite effects results from integrated input of both receptors

intracellular receptors

receptors located inside the cell - molecules must be able to cross mem

plasma membrane receptors

ligand binding is extracellular - for molecules that can't cross mem (majority)

ligands

molecule that binds specifically to receptor site of another molecule

where are intracellular receptors found ?

cytoplasm or nucleus - those in cytoplasm translocated to nucleus upon activation

example of intracellular receptors

steroid hormones

anastrozole

aromatase inhibitor
reduces levels of oestrogen
used to treat breast cancer in post-menopausal women

homology

similarity in structure

how are steroid hormones activated

ligand binding to activation function domain allows receptor to dissociate away from chaperone proteins and dimerise
dimer = active receptor which translocates to nucleus

"zinc fingers"

protrusion on receptor of positively charged amino acids caused by binding of zinc ion (+)

purpose of zinc fingers

allow protein to dock to negatively charged DNA backbone

response elements

region of DNA that binds to receptor recognition sequence on receptor

mechanism of ligand gated ion channel

non-selective cation channels that open in response to ligand binding

cytokine

protein made by certain immune and non-immune cells and has an effect on immune system

leptin

hormone produced by adipose cells that acts as a satiety factor in regulating appetite

kinases

enzymes that catalyse transfer of phosphate groups from ATP to acceptor molecules

RTK

receptor tyrosine kinase

JAK STAT pathway

1x leptin binds to 2x receptors
leptin binding causes dimerisation of 2 receptor
JAK (kinases) partner protein bound to leptin - phosphorylate adjacent receptors
allows STAT to bind and them dimerise themselves (stat-stat)
passes into nucleus, alters gene expression levels

difference between mechanism of intracellular and extracellular receptors

intracellular usually have genomic effects
extracellular usually change protein phosphorylation so effects are faster

4 domains of RTK

extracellular ligand-binding
single transmembrane
cytoplasmic tyrosine kinase
regulatory

SH2

Src homology 2 domain
binds to phosphorylated tyrosine

SH3

binds proline rich sequences

G protein

GTP-binding protein

mechanism of G protein activation

3 subunits - alpha,beta,gamma
bound to GDP
when activated replaced with GTP
alpha subunit dissociates with GDP

mechanism of G protein de-activation

overtime GTP hydrolysed, inactivating complex
alpha unit re-associates with beta and agama

RGS

regulator of G protein signaling
increases rate of hydrolysis of GTP to GDP on alpha subunit

the JAK STAT pathway is involved in…

allergic responses

epinephrine

adrenaline - neurotransmitter AND hormone

role of interleukins

regulate immune response