Signalling Flashcards
Name some things cells may receive signals from
nutritional status, oxygen supply, temperature, pathogens, other cells, hormones, growth factors, pro-apoptotic factors
Name some general responses cells may conduct when signalled
die, grow, divide, differenciate, migrate, change shape, change cell activity, produce new proteins, transcribe new genes, release hormones
name 4 reasons/examples why cell signalling is important
coordinating development (fetal)
maintaining normal physiological functions (homeostasis)
diseases can be caused by abnormal signalling pathways (diabetes/cancer)
many drugs work by targetting signalling proteins (salbutamol)
name 3 examples of signal types and examples for each
physical (pressure/temp)
electrical (nerve cells)
biochemical (hormones, growth factors, neurotransmitters)
in what 2 ways can biochemical signals be classified?
chemical structure and range of action (distance)
name 3 types of hormones and examples for each
animo-acid derivatives (adrenaline/peptide hormones)
steroid hormones, derived from cholesterol (testosterone)
eicosanoids, derived from lipids (prostaglandins)
name the 4 classes of action range in signalling cells
long distance (endocrine - via blood)
nearby cells, by diffusion (paracrine)
neighbouring cell, via cell-cell contact (juxtacrine)
same cell (autocrine)
explain the common 3 stages for all signals
detect sign stimulus
transduce the signal from site of detection to part of the cell that will respond
respond - must be coordinated with responses to other signals; and with responses of other cells (tissue/organ/body)
what are intracellular receptors?
hydrophobic signal molecules that can diffuse through plasma membrane into cell
(steroid hormone, nitric oxide gas)
how do steroid hormones signal?
binds to intracellular receptor proteins
hormone-receptor complex acts as a transcription factor
complex binds to DNA and alters gene expression
how do hydrophilic molecules signal?
using a cell surface receptor protein
(insulin, adrenaline)
name the 3 main types of cell surface receptors
ion channel linked
G-protein linked
enzyme linked
describe the ion channel linked receptors
ion flow into cell changes electrical properties of cell, such as nerve impulse transmission
(e.g glutamate neurotransmitter)
describe the G-protein linked cell surface receptors
activated g-protein activates enzyme that passes on the signal into the cell
very large heterotrimeric g-protein (3 subunits) or small monometric g-proteins
example - adrenaline, seratonin
describe the enzyme linked cell surface receptor function
when signal binds to inactive receptor, the 2 receptor subunits combine, activating the enzyme that signals for a change in the cell
key subtype = receptor tyrosine kinases (RTK)
example - growth factors, insulin
explain the 4 steps involved with RTK binding in enzyme linked receptors
singal dimer binds, kinase activity is stimulated, tyrosines are phosphorylated, intracellular proteins bind to phospho-tyrosine docking areas
describe the process of signal amplication
one receptor molecule activates many relay molecules
different receptors use different transducers/amplifiers
done either by enzyme cascades or second messengers
explain enzyme cascades (specifically MAPK) cascades
activated in response to growth factors (RTK activation)
produces relay proteins Grb/Sos which activates RAS (proto-oncogene)
RAS activates a ‘MAPK cascade’
cascade signal amplified
explain second messengers
second messenger = small molecule produces in large amounts inside cell after receptor activation (cAMP)
second messenger coordinates cell response
(e.g adrenaline, GPCR -> cAMP -> PKS activation -> effector proteins phosphorylated)
what are the general (not always) pairings for different amplication processes?
RTK = MAPK activation
GPCR = second messengers
name 4 molecular level signal responses
gene expression
protein activity (phosphorylation)
protein binding (inhibitor/activator)
protein localisation (transcription factor activated by moving from cytosol to nucleus)
explain the RTK pathways in cancer and treatment
RTK pathways often overactive in cancer, activating mutation or overexpression of RTK or other pathway proteins
treatment - inactivating antibodies or small molecule kinase inhibitors
describe g protein coupled receptor activation (GPCR)
ligand binds to receptor, conf. change in cytoplasmic domain, conf. change allows g-proteins to bind and be activated by receptor, activated g-protein activates intracellular enzymes
explain how the g-protein in GPCR works
GTP is similar to ATP (energy source)
GTP-bound: active
GDP-bound: inactive
activated g-protein activates downstream effector proteins
GAP/RGS proteins = ‘off switch’
describe the effects of GPCR activation
can activate or inhibit intracellular enzymes or proteins directly
production of second messenger molecules
explain how adrenaline is signalled by GPCRs to release glucose
in muscle/liver cell, adrenaline binds to GPCR, the activated g-alpha subunit will activate adenylyl cyclase molecule, activating cAMP which activated PKA
PKA activates glucose production by phosphorylase/kinase and inhibits glycogen storage by synthase
explain multiple signalling pathways
one receptor can activate multiple signalling pathways, one signalling pathway can activate multiple different responses
(e.g EGF receptor for survival, proliferation and invasion)
explain multiple signal integration through p53
the level of DNA damage (genotoxic stress) determines the signalling pathway
mild stress phosphorylates p53 at ser15 causing cell cycle arrest, severe stress phosphorylates p53 again at ser46 causing apoptosis
how does adrenaline show specificity in signalling?
multiple pathways and functions:
- glucose release from skeletal muscle/liver
- increases HR/force
- blood vessel vasodilation/vasoconstriction
- bronchodilation
how (molecularly) can adrenaline signal different specific responses?
can bind multiple GPCRs
multiple g-proteins each binding to GPCRs
multiple second messengers and protein kinase transducers (adenylyl cyclase subtypes)
multiple target proteins
what factors influences a cells response to a given signal?
levels/types of receptor, transducers and effectors expressed in that cell type
genes same; expression differs, meaning the same hormone can have different effects in different tissues
