Lecture 1 Introduction, Cell signalling
Cell-cell communication: extracellular signal molecule binds to receptor protein → intracellular signal proteins →
effector proteins → effects (altered metabolism/altered gene expression/altered cell shape or movement).
Ways of cell communication:
Place of action:
➢ Receptors on cell surface
➢ Intracellular receptors
Signal molecules act:
➢ Contact-dependent (signal molecule-receptor)
➢ Paracrine (cell secretes to different cells)
➢ Synaptic (through neurotransmitters)
➢ Endocrine (through the blood)
The effect of the signal can be fast or slow:
➢ Fast (sec to mins): by intracellular signalling
pathway → altered protein function
➢ Slow (mins to hrs): by altered protein
synthesis.
→ altered cytoplasmic machinery → altered cell
behaviour.
Cell depend on different signals:
No signals → apoptosis
E.g. lung cells get signals from other lung cells. When a lung cell detaches and translocates, it doesn’t get signals
from other lung cells anymore and the cell dies.
In cancer cells, this system doesn’t work well anymore.
Different cells can react differently on the same signal molecule:
➢ ACh in the heart → decreased heart rate
➢ ACh in salivary gland cell → secretion of saliva
➢ ACh in skeletal muscle cell → contraction
,Types of signal molecules and their transduction:
1) Hydrophilic signal cell surface receptor
2) Hydrophobic signal intracellular receptor
3) Gas
- Hydrophilic proteins can not pass the plasma membrane (more common)
- Hydrophobic proteins can pass the plasma membrane → activate
intracellular receptors, mostly inside the nucleus.
2) Hydrophobic signals:
➢ Cortisol
➢ Oestradiol (steroid hormone)
➢ Testosterone (steroid hormone)
➢ Vitamin D3
➢ Thyroxine (thyroid hormone (schildklier) activates basal metabolism)
Low levels iodine → low levels of thyroxine → struma
➢ Retinoic acid
Struma (krop): enlargement of thyroid because of insufficient iodine in food → low levels of thyroid hormone (iodine
is part of the thyroxine molecule)
Nuclear receptors (receptors for steroid hormones):
Left: inhibitory conformation by inhibitory proteins.
Right: steroid hormone ligand (orange) binds → blue part binds around the ligand → inhibitory protein detaches →
active proteins can bind to a specific DNA element → transcription of target gene.
,Nuclear receptors; the chicken and the rooster:
Chicken:
➢ Oestradiol binds to oestradiol receptor (OR).
➢ OR binds to specific DNA in liver.
➢ Induces expression of ovalbumin gene (main protein in white of egg).
➢ Transport ovalbumin to oviduct and egg.
Rooster:
➢ Has no oestradiol but testosterone.
➢ Testosterone binds to testosterone receptor (TR).
➢ TR binds to different part of DNA.
➢ Expression proteins for rooster-behaviour.
Modified rooster:
➢ Replace DNA-binding domain of TR by DNA binding domain of OR.
➢ Testosterone activates this hybrid receptor.
➢ Hybrid receptor binds to DNA for OR.
➢ Thus, testosterone induces ovalbumin in liver rooster.
➢ (The rooster doesn’t lay eggs, because it has no oviduct).
3) Gas; NO (nitric oxide) radical:
Relaxation smooth muscle, improved blood circulation.
Nitric oxide has an unpaired electron. It’s very reactive to get an extra electron.
Acetylcholine activates NO synthases (NOS) in endothelial cell of blood vessel → rapid diffusion of NO across
membranes → NO bound to guanylyl cyclase (uses their electron) in smooth muscle cell (GTP → cyclic GMP) → rapid
relaxation of smooth muscle cell → dilates blood vessels → improved blood circulation.
Because NO is very small, so it can diffuse very fast and is not hindered by membranes.
1) Acetylcholine activates NO secretion by the endothelial cell.
2) Some NO molecules use an electron from guanylyl cyclase and binds to it in an adjacent smooth muscle cell.
3) Guanylyl cyclase is activated and the released cyclic GMP leads to relaxation of the smooth muscle cell
4) Blood vessel relaxes → more blood will flow through the vessel.
, 1) Transduction of hydrophilic signals:
1a) Ion channels
1b) G-protein coupled receptors, second messengers
1c) Protein-protein interactions
MOLECULAR SWITCHES
1) Protein kinases phosphorylate serine, threonine, tyrosine:
The protein kinase adds an phosphate group from ATO
The enzyme phosphatase can remove the phosphate.
Cell-cell communication: extracellular signal molecule binds to receptor protein → intracellular signal proteins →
effector proteins → effects (altered metabolism/altered gene expression/altered cell shape or movement).
Ways of cell communication:
Place of action:
➢ Receptors on cell surface
➢ Intracellular receptors
Signal molecules act:
➢ Contact-dependent (signal molecule-receptor)
➢ Paracrine (cell secretes to different cells)
➢ Synaptic (through neurotransmitters)
➢ Endocrine (through the blood)
The effect of the signal can be fast or slow:
➢ Fast (sec to mins): by intracellular signalling
pathway → altered protein function
➢ Slow (mins to hrs): by altered protein
synthesis.
→ altered cytoplasmic machinery → altered cell
behaviour.
Cell depend on different signals:
No signals → apoptosis
E.g. lung cells get signals from other lung cells. When a lung cell detaches and translocates, it doesn’t get signals
from other lung cells anymore and the cell dies.
In cancer cells, this system doesn’t work well anymore.
Different cells can react differently on the same signal molecule:
➢ ACh in the heart → decreased heart rate
➢ ACh in salivary gland cell → secretion of saliva
➢ ACh in skeletal muscle cell → contraction
,Types of signal molecules and their transduction:
1) Hydrophilic signal cell surface receptor
2) Hydrophobic signal intracellular receptor
3) Gas
- Hydrophilic proteins can not pass the plasma membrane (more common)
- Hydrophobic proteins can pass the plasma membrane → activate
intracellular receptors, mostly inside the nucleus.
2) Hydrophobic signals:
➢ Cortisol
➢ Oestradiol (steroid hormone)
➢ Testosterone (steroid hormone)
➢ Vitamin D3
➢ Thyroxine (thyroid hormone (schildklier) activates basal metabolism)
Low levels iodine → low levels of thyroxine → struma
➢ Retinoic acid
Struma (krop): enlargement of thyroid because of insufficient iodine in food → low levels of thyroid hormone (iodine
is part of the thyroxine molecule)
Nuclear receptors (receptors for steroid hormones):
Left: inhibitory conformation by inhibitory proteins.
Right: steroid hormone ligand (orange) binds → blue part binds around the ligand → inhibitory protein detaches →
active proteins can bind to a specific DNA element → transcription of target gene.
,Nuclear receptors; the chicken and the rooster:
Chicken:
➢ Oestradiol binds to oestradiol receptor (OR).
➢ OR binds to specific DNA in liver.
➢ Induces expression of ovalbumin gene (main protein in white of egg).
➢ Transport ovalbumin to oviduct and egg.
Rooster:
➢ Has no oestradiol but testosterone.
➢ Testosterone binds to testosterone receptor (TR).
➢ TR binds to different part of DNA.
➢ Expression proteins for rooster-behaviour.
Modified rooster:
➢ Replace DNA-binding domain of TR by DNA binding domain of OR.
➢ Testosterone activates this hybrid receptor.
➢ Hybrid receptor binds to DNA for OR.
➢ Thus, testosterone induces ovalbumin in liver rooster.
➢ (The rooster doesn’t lay eggs, because it has no oviduct).
3) Gas; NO (nitric oxide) radical:
Relaxation smooth muscle, improved blood circulation.
Nitric oxide has an unpaired electron. It’s very reactive to get an extra electron.
Acetylcholine activates NO synthases (NOS) in endothelial cell of blood vessel → rapid diffusion of NO across
membranes → NO bound to guanylyl cyclase (uses their electron) in smooth muscle cell (GTP → cyclic GMP) → rapid
relaxation of smooth muscle cell → dilates blood vessels → improved blood circulation.
Because NO is very small, so it can diffuse very fast and is not hindered by membranes.
1) Acetylcholine activates NO secretion by the endothelial cell.
2) Some NO molecules use an electron from guanylyl cyclase and binds to it in an adjacent smooth muscle cell.
3) Guanylyl cyclase is activated and the released cyclic GMP leads to relaxation of the smooth muscle cell
4) Blood vessel relaxes → more blood will flow through the vessel.
, 1) Transduction of hydrophilic signals:
1a) Ion channels
1b) G-protein coupled receptors, second messengers
1c) Protein-protein interactions
MOLECULAR SWITCHES
1) Protein kinases phosphorylate serine, threonine, tyrosine:
The protein kinase adds an phosphate group from ATO
The enzyme phosphatase can remove the phosphate.
