chapter 8: cell signalling Flashcards

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1
Q

what are the three stages of cell signalling?

A
  1. ligand-receptor interaction
  2. signal transduction
  3. cellular responses
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2
Q

stages of cell signalling

what happens during ligand-receptor interaction?

A
  • target cells possess receptor proteins which are able to bind specific ligands
  • the ligand has a specific 3D configuration that is complementary to the binding site of the receptor
  • binding of the ligand to its receptor generally causes the receptor protein to undergo a conformation change
  • which activates the receptor
  • as a result, the chemical information is transmitted from the extracellular environment into the cell
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3
Q

what are plasma membrane receptors and what binds to them?

A
  • these receptors are embedded on the cell surface membrane
  • they are transmembrane proteins
    signal molecules that bind to plasma membrane receptors include:
  • water soluble/ hydrophilic molecules which cannot interact with the phospholipid bilayer of the plasma membrane to pass through it freely
  • molecules which are too large to pass through the plasma membrane
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4
Q

conformational change which result in direct activation of receptor

what are ion channel receptors/ ligand-gated ion channel?

A
  • ligand-gated ion channel is a type of membrane receptor containing a region that acts as a ‘gate’
  • that opens or closes when the receptor changes shape
  • it regulates the passage of specific ions like Na+ and Ca2+
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5
Q

ion channel receptor

what is the structure of the ion channel receptor?

A
  • ligand-gated ion channel forms a protein pore in the membrane
  • it contaisn an extracellular signal-binding site and a region that acts as a ‘gate’
  • the ‘gate’ opens and closes in response to the binding of ligand to the receptor protein to allow specific ions to flow through the channel
  • hydrophilic channel is also specific to specific ions
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6
Q

ion channel receptor

how does the ion channel receptor interact with its ligand and pass on the signal?

A
  • the gate of ligand-gated ion channel remains closed until a specific ligand binds to the receptor
  • binding of ligand to receptor results in a conformational change in the ligand-gated ion channel
  • causing the gate to open
  • specific ions flow through the ion channel
  • resulting in a change in the intracellular concentration of the particular ion
  • triggering cellular responses
  • once the specific cellular response has been carried out
  • the ligand disscoiates from the receptor
  • causing the ion channel to close
  • this terminates the signal
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7
Q

GPCR

what is a G-protein coupled receptor?

A
  • it is a cell-surface transmembrane receptor that works with the help of G-protein
  • G-protein: a protein that binds to guanine nucleotides GTP or GDP
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8
Q

what is the structure of the GPCR receptor?

A
  • a GPCR consists of seven transmembrane a-helices

each GPCR receptor contains:
- an extracellular ligand-binding site
- a intracellular/cytoplasmic G-protein binding site

the G protein functions as an on-off switch, depending on which of the two guanine nucleotides is bound

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9
Q

how does the GPCR interact with its ligand and pass on the signal?

A

when the G-protein system is inactive, G-protein is bound to GDP

  1. upon binding of the signal molecule on the extracellular ligand-binding site of GPCR, the receptor is stimulated to undergo a conformational change
    > GPCR becomes activated
  2. the cytoplasmic side of the activated GPCR binds to the inactive G-protien, causing a conformational change in the G-protein
  3. GDP is displaced from G-protein by GTP
    > the G-protein becomes activated
  4. activated G-protein binds and activates other effector proteins like adenylyl cyclase
  5. once specific cellular responses have been carried out, GTP is hydrolysed to GDP by the intrinstic GTPase ezyme in the G-protein
    - G-protein leaves effector protein and returns to its inactivated form, ready and availible for reuse again
    - hence, the GTPase function of the G protien allows the pathway to be shut down rapidly
    - when the extracellular signal molecule is no longer present
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10
Q

which structural feature of GPCR gives it this function?

fucntion: it allows GPCR to be stably embedded in the cell surface membrane

A
  • secondary structure with seven transmembrane a-helices
  • the exterior surfaces of the helices have many amino acid residues with non-polar, hydrophobic R groups
  • these amino acid residues face the non-polar fatt acid tails of the phospholipids in the cell surface membrane
  • interacting with the fatty acid tails via hydrophobic interactions
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11
Q

which structural feature of GPCR gives it this function?

function:
- has a complementary shape to the ligand to allow binding of a specific ligand on the extracellular ligand-binding site of the GPCR
- has a complementary shape to the G protein and allows the binding of the G protein in the cytoplasm to the cytoplasmic G protein binding site of the activated GPCR

A
  • transmembrane protein that has specific loops between the a-helices

these loops form these binding sites:
- an extracellular ligand-bindign site
- a intracellular G protein binding site

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12
Q

which structural feature of GPCR gives it this function?

function: to allow binding sites of different GPCRs to have different shapes
> so that a large variety of ligands and G proteins can bind to different GPCRs
> allows different ligands to activate different/ same cell signalling pathways

A
  • eventhough all GPCRs have seven trasnmembrane a-helices
  • the specific amino acid sequences at both the ligand and G-protein binding site differ for different types of GPCR
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13
Q

what is the structure of receptor tyrosine kinase?

A

tyrosine kinase receptor contains:
- an extracellular signal-binding site
- a single a-helix trasnmembrane region
- an intracellular tail containing several tyrosine amino acid residues
> the intracellular tail also functions as tyrosine kinase enzyme

  • in the inactive state, tyrosine-kinase receptors exist as monomers
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14
Q

how does tyrosine kinase receptor interact with its ligand and pass on the signal?

A
  1. when ligand binds to each other of the two tyrosine-kinase receptor monomers
    - the receptor monomers aggregate, forming a dimer
    - dimerisation activates the tyrosine kinasse region on each receptor monomer
  2. each activated tyrosine kinase region phosphorylates the other receptor monomer at the tyrosine residues on the intracellular tail
    - (additions of a phosphate group from an ATP molecule)
    - this fully activates the receptor, forming a phosphorylated dimer
  3. the fully activated tyrosine-kinase dimer binds and activates many specific intracellular relay proteins via phosphorylation
  4. each activated tyrosine kinase dimer can activate many different intracellular proteins simultaneously and trigger many different transduction pathways and cellular responses
  5. after specific cellular responses have been carried out, the signal is termindated via the removal of the ligand
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15
Q

what is a difference between RTK and GPCR?

A
  • one activated receptor tyrosine kinase dimer may activate ten or more different transduction pathways and cellular responses simultaneously
  • RTK: its ability of a single ligand-binding event to trigger so many pathways simultaneously is a key difference from GPCR
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16
Q

what is signal transduction and what are the two main mechanisms?

A
  • ligand-receptor binding intiates a signal transduction pathway inside the cell
  • a signal transduction pathway involves a sequence of changes in a series of relay molecules within the cell, which result in a specific cellular response

two main mechanisms:
- protein phosphorylation
- activation of a second messenger

17
Q

what is protein phosphorylation?

A
  • information is passed from the ligand to intracellular proteins through a series of phosphorylation of intracellular relay proteins
  • upon ligand binding, a relay protein is activated and initiates a phosphorylation cascade
  • many relay proteins are protein kinases and they act on other protein kinases
  • a phosphorylation cascade consists of a series of protein kinases which shuttle between the phosphorylated (active) and dephosphorylated (inactive)
  • each activated protein kinasee phosphorylates its succeeding protein kinase by transferring a phosphate group from ATP to their substrate proteins, activating them
  • the activation of the last protein in the pathway results in a cellular response to the signal
  • in the absense of extracellular signal, the signal-transduction pathway is turned off by protein phosphatases
  • which are enzymes that remove the phosphate groups from proteins
  • by dephosphorylating and inactivating protein kinases,
  • phosphatases provide a mechanism for shutting down the signalling pathway and cellular response
18
Q

what are second messengers and what are the two most common second messengers?

A
  • many signalling pathways also involve small, non-protein water soluble molecules called second messengers
  • the ligand is the first messenger
  • as second messengers are small and water soluble, they can readily spread throughout the cell by diffusion
  • they are responsible for relaying the signal from the cell surface to target moelcules inside the cell in order to elicit specific cellular responses
  • second messengers participate in pathways initiated by both G protein linked receptors and tyrosine kinase receptors

the two most common sencond messengers are
- cyclic adenosine monophosphate (cAMP)
- calcium ions (Ca2+)

19
Q

second messenger

what is cyclic adenosine monophosphate? (cAMP)

A
  • cAMP is made from ATP catalysed by adenyly cyclase, an enzyme embedded in the plasma membrane
  • cAMP is a component of many G-protein signaling pathways as G protein activates adenylyl cyclate
  • the immediate effect of cAMP is usally activation of serine/threonine kinase called protein kinase A
  • the effect of cAMP is short lived
  • it is inactivated by phosphodiesterase, an enzyme that converts it to AMP
20
Q

second messengers

how does the calcium ions function?

A
  • calcium ions can function as second messenger because its concentration in the cytoplasm is much lower than outside the cell
  • cells use Ca2+ as second messengers in both G protein and RTK pathways
  • many signalling moelcules in animals induce responses in their target cells via signal transduction pathways that increase the cytosolic concentration of Ca2+
  • increasing the cytosolic concentration of Ca2+ causes many responses in animal cells
  • like muscle cell contraction, secretion of certain substances and cell division
21
Q

what is signal termination and how can it be carried out?

A
  • after the specific cellular response have been carried out , the signal is terminated
  • signal termination has to be carried out in order for the cell to be continually receptive and sensitive to regulation by signalling

signal termintion can occur by:
- dissociation of ligand from receptor followed by destruction/ inactivation of ligand
- deactivation of a signal transduction protein ( like dephosphorylation of protein kinases by protien phosphatase)
- degradation of second messenger

22
Q

what are the cell signalling pathways that allow for coordination of signalling pathways and also contribute to the specificity of the response?

A
  1. different cells can respond differently to the same ligand-receptor interaction
    - depending on the type of proteins that relay and respond to the signal
    - a single tpe of ligand can trigger different cellular responses in different types of cells at any one time
  2. the same ligand binding to different receptors can also trigger different responses
  3. a pathway that is triggered b a single kind og ligand can diverge to give two different responses
    - a single type of ligand can trigger numerous responses in a cell all at once through activation of multiple transduction pathways
  4. two pathways triggered by seperate signals can converge to modulate a single response
23
Q

INSULIN AND RTK SIGNALLING

describe the ligand- receptor interaction.

A
  • ligand: insulin
  • receptor: RTK receptors on target cells
  • insulin bind to RTK receptors at cell surface membrane
  • dimerisation activates the tyrosine kinase region on each monomer
  • each activated tyrosine kinase region phosphorylates the other receptor monomer at the tyrosine residues on their intracellular tail, fully activating the receptor
24
Q

INSULIN AND RTK SIGNALLING

describe the signal transduction

A
  • fully activated RTK receptors activate a series of protein kinases in a phosphorylation cascade
25
Q

INSULIN AND RTK SIGNALLING

describe the cellular response

A
  • activated intracellular proteins cause vesicles with glucose carrier proteins to move to the cell surface membrane and fuse with it
  • glucose carrier proteitns are inserted into the membrane
  • more glucose carrier proteins along membrane
  • allows for an icnrease in uptake of glucose by cells

other cellular responses:
- increase in activity or synthesis of enzymes involved in glycogenesis, respiration and fat synthesis
- glycogenesis: synthesis of glycogen
- decrease in activity or synthesis of enzymes involved in glycogenolysis and gluconeogenesis
glycogenolysis: breakdown of glycogen
gluconeogenesis: formation of glucose from non-carbohdrate sources

signal termination: after the specific response has been carried out,
- insulin is released from receptors
- dephosphorylation of protein kinases by phosphatase enzymes
- endocytosis of glucose carrier proteins, carrier proteins are removed from the cell surface membrane

26
Q

glucagon and G protein signalling

describe the ligand receptor interaction.

A
  • ligand: glucagon
  • receptor: GPCR on liver cells
  • second messengers: cAMP
  • glucagon binds to G protein couple receptors at the cell surface membrane
  • the receptors undergo a conformational change and the receptors become activated
  • the activated GPCR binds to G protein
  • the G protein undergoes a conformational change causing the GDP to be displaced by GTP
  • the G protein becomes activated
27
Q

glucagon and G protein signalling

describe signal transduction

A
  • activated G protein activates adenlyl cyclase which catalyses the conversion of ATP to cAMP
  • cAMP then activates protein kinase A
  • the activated protein kinase A then phosphorylates other protein kinases in a serries of phosphorylation cascade until it reaches the final protein
  • the final protein to be activated is enzyme glycogen phosphorylase
28
Q

glucagon and G protein signalling

describe the cellular respons

A
  • glycogen phosphorylase casues the breakdown of glycogen to glucose

other cellular response
- increase in activity or synthesis of enzymes involved in gluconeogenesis

singal termination, after the specific response has beeen carried out,
- glucagon is released from receptor
- GTP on G protein is hydrolysed to GDP by intrinstic GTPase enzyme in G protein
- cAMP is degraded to AMP by phosphodiesterase

29
Q

explain why insulin receptors are found on the cell surface membranes of target cells and never within the cells?

A
  • insulin is a large/ hydrophilic
  • and will be repelled by the hydrophobic core made by fatty acid tails of the phospholipid bilayer
  • thus, insulin cannot pass through the cell surface membrane but interact with the receptor by binding to its extracellular ligand binding site
30
Q

what are the advantages of a G-protein signalling pathway?

A
  • Allows for signal amplification, where a single glucagon ligand results in the production of many second messenger molecules, such as cAMP, leading to a large cellular response.
  • Ensures specificity of response, where only glucagon molecules with a complementary shape to the ligand binding site on the GPCR receptor can bind, activating the signaling pathway in specific cells.
  • Provides the ability for control at multiple points to fine-tune the cellular response, as the levels of GTP, G-protein, or adenyl cyclase can be regulated to adjust the overall cellular response.
31
Q

explain the significance of cell signalling pathways.

A
  • Cell signaling pathways allow for cellular responses to maintain a constant internal environment.
  • They enable signal amplification, as each catalytic step activates more products than the preceding one, leading to a larger response.
  • A small number of extracellular signals can trigger a large cellular response.
  • Different pathways can converge to modulate a single response.
  • A single signal can diverge to produce multiple cellular responses.
  • Specificity of response is ensured by the presence of specific receptors and relay proteins in target cells.
32
Q
A