Cell Signalling Flashcards by Anna Safrankova

What is cell signalling for

Controlling a cells behaviour.
It induces a response in a cell

Eg gene expression, structual change, enzyme activity

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Give examples of where cell signalling is important

The nervous system (electrical signals)

Immune system - WBCs / antigens

Cell cycle

Metabolism- controlling blood glucose (via adrenaline/insulin)

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what are the 5 steps of cell signalling and the proteins involved / molecules

Signal - messenger/ligand

Reception - detection by receptors

Transduction - transducer proteins

Amplification - secondary messengers/ cascades

Response - effectors eg enzymes/ transcription factors

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What is transduction

Conversion of a signal to another type of signal by transducer proteins

To pass info down pathway

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Name 2 ways protein activity in signalling pathways are altered (switching)

1- conformational change can switch on and off

2- covalent modification

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What is covalent modification/ example of how it alters proteins in signalling pathways

Proteins can be switched on and off by adding of molecules

Eg phosphorylation

Kinase will phosphorylate a protein

And to switch it off phosphatase switches it off by removing phosphate

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Name some signals / Ligands cells respond to

Physical signals - light, heat

Chemical - hormones, NTs, antigen, nitrous oxides gases

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Name the 4 local signalling methods (short distance)

1- gap junctions

2- contact dependant

3- para crine

4- autocrine

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How does gap junction signalling work ?

Small signalling molecules such as ions and metabolites (ATP,camp, iP3)

Pass cell to cell through connexon hemi channels

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What are the channels called in gap junctions between cells

Connexon hemichannels

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How does contact dependant signalling work

When cells nearby each other can form surface receptor/signalling molecule complexes

Eg in immunity these are antigens and receptors

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How does paracrine and autocrine signalling work

Paracrine - signalling cells will release local mediator signal molecules/ ligands and then nearby cells will bind to them via receptor = response induced

Autocrine- where cells will release local mediator signal molecules themselves and then bind to the molecules via receptors they released

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Give example of local mediator signals in paracrine signalling

Cytokines and growth factors (for proliferation)

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Name the 2 major distant cell signalling methods

Synaptic signalling (neurone to neurone via Nts)

Endocrine signalling - via hormones in the blood stream

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Cell receptors can be intracellular. Name 2 examples

Nuclear hormone receptors (ligand induced transcription factors)

Nitric oxide receptors (guanylyl)

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How does nuclear hormone receptors work - how are they transcription factors (regulating transcription)

When a hormone binds to the receptor on the ligand binding domain this causes a conformational change

This allows the ligand- receptor complex to enter nucleus and bind to dna (via dna binding domain) and initiate gene expression

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How are nitric oxide receptors (guanylyl) an intracellular receptor allowing cell response?

When nitrous oxides diffuse across and bind to GUANYLYL RECEPTORS

This causes a conformational change

This causes GTP to be converted into cyclic GMP

Cyclic gmp secondary messenger causes muscle dilation/ relaxation

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What would happen if cells didn’t have receptors for the signals?

No response would be induced by the cell

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How is androgen insensitivity syndrome an example of receptor importance

They have no androgen binding receptors that bind to steroids like testosterone

If males don’t have them they develop as a female male due to testosterone having no effect

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What are the 3 types of cell surface receptors

Ion channel coupled receptors / ligand gated

G protein coupled receptors

Enzyme coupled receptors

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Give an example of ion channel coupled receptors

Nicotinic AcH receptors on synapse which change in confirmation to allow Na to flow through

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Why are G protein coupled receptors called 7 pass transmembrane receptors

They’re made of 7 alpha helixes which pass the membrane 7 times (embedded in membrane)

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What are the 2 types or transducing G proteins

Trimeric - transduce signals from G protein receptors

Monomeric - transduce signals from enzyme linked receptors

Name the 3 parts of a trimeric G protein

3 subunits

Alpha subunit (Ras) is where GDP or GTP bind

Beta and gamma subunits dissociate from alpha when the protein is activated

Explain what happens when a signal molecule binds to a trimeric g coupled protein receptor

The signal causes a conformational change causing alpha subunit to release its GDP molecule This allows for GTP to bind When GTP is bound the alpha subunit dissociates as it is activated The alpha subunit then moves to activate target proteins

What does alpha subunit do when activated

The subunit binds to a target protein and transduces a signal to the protein The protein then detaches away from subunit when GTP is hydrolysed back into GDP and P The subunit is then inactivated and reassembles to B and gamma subunit

What are Ligands

Molecules that bind to intracellular receptors such as testosterone and cortisol

Why are the 2 main proteins targeted by the trimeric G protein and what secondary messengers do they produce when activated

Adenylate Cyclase - cyclic amp Phospholipids C - ip3

Explain the whole cascade of events when adrenaline binds to muscle or liver trimeric G protein coupled receptors This activates conversion of glycogen into glucose for flight or fight response

When it binds the conformational change in the G protein occurs The alpha subunit then targets the adenylate cyclase and activates it (transduces the signal) The adenylate cyclase then converts ATP into cAMP cAMP activates protein kinase A Protein kinase A then causes causes phosphorylation by activating phosphorylase kinase This leads to phosphorylation of enzyme phosphorylase A Leads to breakdown of glycogen into glucose

Why is cascades for amplification important for cell signalling

It causes a faster response by the cell

What does cAMP dependant protein kinase do when camp activates it

Undergoes a conformational change where the catalytic subunits are released to allow phosphorylation of phosphorylase kinase

Which 2 secondary messengers are produced by phospholipase C (activated by trimeric G proteins)

IP3 and DAG

What happens to phospholipids when phospholipase C is activated?

PIP2 phospholipids are cleaved (cut) Produces DAG and IP3

What is IP3s role in cell response

IP3 binds to calcium channels on the ER of a cell Calcium is used then to activate proteins

How does calcium and calmodulin protein cause activating of kinase C?

The calmodulin protein binds to 4 ca2+ and this causes a conformational change This calcium- calmodulin complex wraps on target proteins eg PKC = activated

What is DAGs role in PKC - cell response

DAG is membrane bound and allows PKC to stick there. This allows for the phosphorylation of proteins = cell response

What 2 things do enzyme coupled receptors need for activation

Dimerisation and phosphorylation (eg in RTKs) | Dimerisation just means bringing subunits together of the receptors

What 2 things do receptors called enzyme coupled need to be enzyme coupled

1- intrinsic enzyme activity 2- associated with an enzyme to catalyse a reaction

Receptor tyrosine kinases (RTKs) are a group of enzyme coupled receptors. What molecules do they usually bind with?

Growth factors (which control cell proliferation- RTKs are v important)

What does binding of the growth factor of RTKs cause

Leads to autophosphosphorylation and dimerisation of the receptor (2 subunits are brought closer together)

Why doesn’t dimerisation occur with insulin receptors (also RTKs)

Because insulin is already a tetramer of polypeptides They just auto phosphorylate instead

How does auto phosphorylation of RTKs like Ras allow for activation of cell signalling pathway proteins?

The proteins associated with it (monomeric G proteins) are activated by the phosphorylation

What is Ras

A monomeric G protein which is activated by the RTKs (when growth factors bind)

What do monomeric G proteins do?

Transduce signals from the enzyme coupled receptors Eg Ras from the RTKs

What 2 proteins do monomeric G proteins need for the activation and the deactivation of the G protein (trimeric don’t need these)

GEF- guanine exchange factor GAP- GTPase activation protein

What is GEF needed for by monomeric G proteins

Guanine exchange factor Needed to activate release of GDP(so it can be activated)

What is GAP needed for by monomeric G proteins like Ras - needed to deactivate the protein

GAP Needed for the aid of GTP hydrolysis back into GDP aswell as GTPase (too weak on its own)

Explain the steps of the activation of the Ras monomeric G protein when growth factors bind to RTK

RTK when phosphorylated and dimerised The adaptor protein GRB2 binds to it This then allows GEF to stimulate GDP release from Ras monomeric protein GTP instead is added to Ras G protein This then is activated

What is the phosphorylation cascade that Ras activates called and what are the 3 components

MAP kinase cascade MapKKK - RAF MAPKK - MEK MAPK - ERK Proteins in nucleus (MAPs)

Explain the steps from Ras activation to the phosphorylation of proteins in the nucleus

Ras protein when activated Activated RAF mapKKK RAF KKK phoshphorylates MEK MEK phosphorylase ERK ERK translocates into nucleus ERK phosphorylates proteins in nucleus Proteins that activate gene transcription of for example cyclin production = allow cell division/proliferation

What is Ras in terms of cancer?

It’s a protooncogene (because it controls cell proliferation)

What happens when Ras has mutations (cancer)

GTP hydrolysis is inhibited Ras stays active Signalling switched on constantly Cell proliferation

What do inhibitors targeting the Ras and map K cascade do?

Stop cell proliferation

What does single pass transmembrane proteins mean?

Their helixes only passes membrane once

Apart from acH, what other ligand hormone acts differently on diff cells

Adrenaline at muscle cells causes glycogenolysis At heart cells they cause increased heart rate

Why does epinephrine cause heart contraction in contrast to acetylcholine

Epinephrine causes presence of camp from activation of adenylate cyclase when epinephrine hormone binds to heart muscle