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Cell Signalling
CS1
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Hormones, amino acids, etc
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• G-protein-coupled receptors

• Enzymatic receptors (receptor tyrosine kinase)

• Chemically-gated ion channels

Signal Transduction
• Refers to a series of changes in cellular proteins that converts extracellular chemical
signals into a speci c intracellular response, such as by activating other relay
proteins through a phosphorylation cascade and signal ampli cation

A phosphorylation cascade is a sequence of events where one enzyme phosphorylates
another, causing a chain reaction leading to the phosphorylation of thousands of proteins
...
Kinase (an enzyme) adds phosphate groups from ATP to the protein and
activates them, while phosphatase (an enzyme) removes phosphate groups from proteins
via hydrolysis to deactivate them
...
Protein kinases are
usually involved since they catalyse the phosphorylation of speci c proteins to activate
them
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If growth factors
are not removed, excessive cell proliferation will take place, resulting in the formation
of a tumour)

CS2
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Types of Receptors

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G-Protein Coupled Receptor (GPCR)
• Transmembrane protein consisting of 7 a-helices connected by 3 intracellular and 3
extracellular peptide loops

• Has an extracellular ligand-binding site that binds to speci c hydrophilic ligands (eg
...
)

• Intracellular domain has a G protein binding site that allows the binding of a G protein
complex

• G proteins have intrinsic GTPase activity and are capable for hydrolysing GTP to GDP
(inactive when GDP is bound to it, active when bounded to GTP)
...
The continued activation could render the
cell unable to respond to other signals or to respond inappropriately to a signal that is
no longer relevant


• Small and water-soluble secondary messengers which is di use throughout the cell

readily such a cAMP can help to activate cellular proteins

Having the 3 proteins in the GPCR system attached to the plasma membrane increases
chances of these proteins interaction due to close proximity and restriction of
movements


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Glucagon and G-protein signalling
• Glucagon binds to the ligand-binding site of the glucagon receptor to induce a
conformational change in the intracellular domain of the receptor

• GTP will replace GDP on the G protein to activate it
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Increased cAMP
levels will result in the activation of protein kinase A (PKA) which will activate
phosphorylase kinase that will in turn phosphorylate glycogen phosphorylase,
converting it to active form
...


• PLA also inactivates glycogen synthase and inhibits glycogen production

Receptor Tyrosine Kinase (RTK)
• Cytoplasmic part of the receptor has a tyrosine kinase which phosphorylates the
tyrosine resides (intrinsic kinase activity)

• Dimerisation of 2 receptor subunits into a pair when a ligand binds to the ligandbinding site

• Conformational change in the intracellular domain of the receptor activates tyrosine
kinase, tyrosine residues will cross-phosphorylate each other via intrinsic kinds activity

• Phosphorylated tyrosine residues are activated and can recruit speci c relay proteins

Insulin and RTK signalling
• Insulin receptor is an RTK that exists as a linked dimer

• Binding of insulin to the ligand-binding site of the receptor induces a conformational
change in the intracellular domain of the receptor, which leads to the crossphosphorylation of tyrosine residues

• Activated insulin receptor tyrosine kinases can phosphorylate and recruit di erence
intracellular signal proteins which can activate di erent intracellular pathways

• Cellular responses include induction of glycogen synthesis via activated glycogen
synthase and stimulation of glucose uptake in muscle and adipose tissues via the
translocation of vesicles containing GLUT4 transporters to the plasma membrane

• GLUT4 transporters increases the membrane’s permeability to glucose and increases
glucose uptake


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Chemically-gated ion channels
• Receptor Proteins an serve as an ion channel, where the receptor is activated by the
binding of a chemical ligand to induce a conformational change that results in the
opening or closing of an ion channel

• Flow of ions across the cell membrane results in a temporary change in membrane
potential, a ecting the activity of other membrane proteins to trigger a cellular
response


CS4
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A gain-in-function mutation would result in proteins that have increased function
...
This could result in cells
dividing excessively, without the presence of appropriate signals, causing
uncontrolled cell division

2
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For example, the
gene coding for protein kinase could be non-functional such that it is unable to
activate the next protein kinase
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