1: L6 Flashcards
How do cells respond to their environment? (5 ways)
- Signalling: chemical (molecules cell receives) and mechanical
- Receptors
- Intermediaries – influencing post translational modifications
- Nuclear translocation/nuclear import
- Most pathways end with the nucleus and gene regulation
examples of chemical messenger types used in signalling
growth factors, hormones, neurotransmitters, extracellular matrix components
2 types of receptors
- Membrane bound proteins, OR
2. Intracellular receptors
How do Intracellular receptors work
if the signal is lipid soluble (gases, steroid hormones i.e. estrogen) = moves thru membrane in cytoplasms
• Once bound by substrate, receptors move into nucleus + regulate gene expression
Example of a intracellular lipid soluble signal
Estrogen
- dimerizes inside cytoplasm
3 examples of membrane bound receptors
GPCR (g protein coupled receptor)
Ion channel receptor
Receptor Tyrosine kinases
Describe process of GPCR
- Most market drugs target GPCR
o Ligand (the chemical signal) will dock on extracellular surface of GPCR
o Receptor changes confirmation
o Changing conf activates G protein underneath it (cytoplasmic surface)
o GDP (on g protein) switched for GTP = active and therefore activates required other proteins - Once bound to GTP, the G protein alpha activates effector enzymes that then trigger a signalling cascade
Is GPCR an applification point and what is it
yes
= amplification point notas one ligand= one receptor but active g proteins activate many other molecules
describe ion channel recptor
- Doesn’t have big signalling cascade dependant effects
- Simpler receptor where ligand passes through
- Confirmation changes open/closed
- Important in nervous system
describe what a kinase and tyrosine kinase is
• Kinase: adds phosphate groups (activates)
- // tryosine kinases adds phosphate to tyrosine
how does a Receptor Tyrosine Kinases work w/ example
E.g. EGFR -Epidermal growth factor receptor
o EGF (ligand) binds to receptor= dimerization of the receptors (physically move together in the membrane)
o Activates tyrosine kinases activity in cytosolic side of receptor
- Ability to add phosphates= inherent in cytosol structural part of the receptor (catyolic enzymatic part) i.e. phosphorylates itself + // allows activation (phosphorylation is detected by other molecules)
name example of • Post-translational modifications + importance
phosphorylation = transmitting signal through secondary messengers
Description of Secondary messenger PI3K
- PIP2 to PIP3 is addition of phosphate= activation
- PTEN= regulation (removes 1 phosphate to switch off system)
• PTEN a common mutated protein in cancer
Describe JAK-STATE signalling
- Ligand binding
- receptor dimerisation brings two JAK (which is on receptor) to proximity > trans-phosphorylation
- STATs phosporlyated by JAKs
- pSTAT dimerises
- pSTAT translocate to nucleus
- pSTAT activates transcription
how is beta catenin kept at low levels
- Constantly degraded by proteasome
- Targeted by molecule APC Axin + sends towards proteasome
