Flashcards
Introduction Into Cell Signalling
Cards in this deck (116)
- 1Why do cells need to signal?Co-ordination of function
- 2What does the ability do cells require to survive?Ability to respond to continuous signals
- 3What are the two general cell signalling pathways?1) Extracellular signal acts on a receptor
2) Intracellular signal is transduced
resulting in:
a) gene expression in the nucleus and new protein production
or
b) metabolism/muscle contraction - 4Which type of signalling pathway is slow and which is fast?Production of new proteins is relatively slow and metabolism/muscle contraction is fast
- 5What are the broad terms for molecules through the signalling pathway?1) Extracellular signal molecules
2) Receptor protein
3) Intracellular signalling protein
4) Effector proteins - 6Give three examples of effector proteins and their function1) Metabolic enzymes - altered metabolism
2) Gene regulatory protein - altered gene expression
3) Cytoskeletal protein - altered cell shape or movement - 7List 7 intracellular effector proteins1) Protein kinases/phosphatases
2) Lipid kinases/phosphatases
3) GTP binding protein
4) Diffusible mediators
5) Enzymes
6) Transcription Factors
7) Adaptors - 8What is the function of protein kinases/phosphatases? What else can kinases do?1) Kinases phosphorylate proteins changing their function. Kinases can also activate other kinases by phosphorylating them
2) Phosphatases dephosphorylate proteins -usually inactivating them - 9Give two examples of diffusible mediatorsCalcium and glycerol
- 10What is the function of GTP binding molecules?Activate GTP signalling cascade
- 11What do adaptors do? How do they achieve this?Adaptors activate the proteins they are bound to when they are phosphorylated.
- 12What is the usual response to: Pupils to light? Heart to exercise? Damage to vessels? Temperature to infection?1) Dilation
2) Increase HR
3) Clotting
4) Fever - 13What does cancer result from?Increased activity of constituent pathways can lead to increased cell survival and proliferation resulting in the formation of a tumour
- 14What are the three types of cellular communication?1) Cell to cell
2) Cell to neighbouring cell(s) - autocrine/paracrine
3) Cell to distant cell - endocrine - 15What does cell to cell communication require? What different methods can it use?1) Contact
2) Electrical via gap junctions or receptor and ligand (chemical) - 16Over what distance is autocrine/paracrine signalling used?Short distances
- 17What two type of signalling are used in long distance signalling?Endocrine - chemical signals such as hormones diffuse into the blood
Electrical - AP through long axons - 18Give an example of electrically coupled cells? What is the function of this?1) Heart cells - gap junction allow small ions and metabolites to pass through
2) Allows for simultaneous contraction - 19Give an example of ligand contact signalling.T cell receptor CD26 recognises CD80/CD86 on APC
- 20What are the targets of ligands released from cells?1) Cell surface receptors
2) Intracellular receptors - 21What qualities must ligands which target intracellular receptors have? (3)1) Small
2) Hydrophobic
3) Able to find target - 22Give two examples of cells which operate in an autocrine/paracrine manner and their function1) Mast cells - Release histamine to cause an inflammatory response, increase vasodilation and mast cells, recruit eosinophils
2) Endothelial cells produce NO to cause vasodilation and keep platelets inactivated - 23What determines whether a cell responds to endocrine signalling?Receptor expression
- 24What does the effect of neurotransmitter depend on?The type of cell activated
- 25Define ligandA molecule which can bind to a receptor
- 26Define intracellular signallingIntracellular reactions elicited by receptor activation that cause and effect
- 27What usually are the effects of cell activation?Cell function, cell growth, cell differentiation
- 28What are the two changes which usually occur as a result of cell stimulation? What do they result in?1) Altered protein function (rapid effect) and synthesis (slow)
2) Altered cytoplasmic machinery and therefore cell behaviour - 29What is the difference between endocrine, neurocrine and synaptic signalling?1) Endocrine in from cell to blood
2) Neurocrine occurs when stimulation of a neuron results in the release of a transmitter into the blood
3) Synaptic is when a neuron is stimulated, the signal travels down a axon resulting in release of neurotransmitter very close to the cell - 30Give an example of Cell to cell signalling: Gap Junctions? Receptor-ligand?1) heart cells
2) drosophila eye - neighbouring proteins allow fly to detect UV light - 31When is autocrine signalling common? What pathology does it underlie?1) Developmental or differentiating cells
2) Tumour cells where they produce growth hormones which stimulate uncontrolled growth and proliferation - 32Why is paracrine signal distance limited? Give an example of paracrine signalling1) Signalling molecules rapidly destroyed by enzymes or taken up by cells
2) Neurotransmitters from cells - 33Describe the features of endocrine signalling (3). What determines the ability of cells to detect their target?1) Transported in blood, slow, non specific
2) Tissues bathed in a substance, cells/ligands must be able to detect specific substance coating target - 34How does electrical signalling work?AP propagates along neuron
- 35What effect does acetylcholine have on: 1) Heart muscle? 2) Skeletal muscle? 3) Smooth muscle? 4) Salivary glands?1) Decreased rate and force of contraction
2) Increased contraction
3) Increased contraction
4) Secretion - 36What three things are responsible for the variation of response to a single signalling molecule? Give examples1) Different receptors (ie heart and skeletal)
2) Same receptors, different signalling pathways (ie heart and smooth)
3) Same receptors, same signalling pathway, different protein receptors (ie heart and glands) - 37What effect does adrenaline have on the heart? lungs? arteries to muscle? peripheral arterioles? Muscle and liver?1) Increased HR and force of contraction
2) Relaxation in airways
3) Dilation/relaxation
4) Constriction
5) Glycogen break down - 38What is the net effect of an increase in adrenaline?Increased glucose, increased O2 available, increased circulation to muscles -- increase physical capabilities
- 39In which three ways can signalling molecules exist?1) Soluble and mobile
2) Fixed to extracellular matrix - ie collagen fibres after muscle damage
3) Attached to outer cell surface - 40What are four important properties of signalling molecules?1) Control of synthesis, degradation and removal
2) Solubility
3) Active at low conc.
4) Lifespan - both of the signal and the effect - 41What are the three types of receptors involved in cell signalling?1) Cell Membrane
2) Cytoplasmic
3) Nuclear - 42What are the types of cell membrane receptors?1) Ligand-gated ion channels (ionotropic)
2) G-protein coupled (metabotropic)
3) Enzyme-coupled - 43Give an example of a cytoplasmic receptor and what its activation leads to.Guanyl cyclase, stimulated by NO leading to vasodilation
- 44What do nuclear receptor effect? Give three examples. What do they all do?1) DNA/RNA/protein expression
2) Steroid hormones, thyroid hormones and vitamin D
3) All bind to receptors in the cytoplasm which regulate gene expression. Structurally related ie the steroid super family - 45What are nicotinic acetylcholine R, GABAaR and P2x purinoceptors?Ionotropic recptors
- 46What are a & B adrenergic R, mAChR, GABAbR and mGluR?Metabotropic Receptors
- 47What are the two types of enzyme coupled receptors?Either dimers or monomers
- 48How do dimers activate enzyme-coupled receptors?Binding activates catalytic domain resulting in cross-phosphorylation and dimerisation of the receptor.
- 49How does a monomer activate an enzyme couple receptor?Molecule binds causing receptor halves to join (each is half the binding site), activating the associated enzyme
- 50Give an example of a receptor tyrosine kinase.Vascular endothelial growth factor
- 51Give an example of receptor guanyl cyclase.ANP receptor
- 52Give an example of receptor linked kinase receptorsCytokine receptors
- 53How is a ligand-gated ion channel activated? What does this result in? What drives the ion flow? Give an example and what happens when this channel is stimulated?1) By extra- or intra-cellular ligand.
2) Opening (although sometime closing) of channel
3) Ionic gradient and channel selectivity
4) nAChR, ATP-sensitive K+ channel, muscle contraction. - 54What happens as an action potential travels down an axon? What does this have on postsynaptic muscle fibres?Opens VG Na+ channels = propagation. Reaches VG Ca2+ channel at axon terminal. Entry of Ca2+ causes translocation and release of neurotransmitter into synaptic cleft. Activation of ligand gated Na+ channels then voltage gated Na+. Leads to activation of VG Ca2+ channels. Ca2+ in muscle fibres leads to contraction.
- 55—1) VG Ca2+ channel
2) LG Na+ channel
3) VG Na+ channel
4) VG Ca2+ channel
5) Ca2+ gated Ca2+ channel - 56How is visual information transduced?Opsins use a photoisomerization reaction to translate light into cellular signals via activation of a GPCR
- 57Which other senses use GPCRS?Taste
Olfaction (olfactory and vomeronasal receptors) - 58How are mood and behaviour regulated?Receptors in mammalian brain bind several different neurotransmitters including serotonin, GABA, glutamate and dopamine
- 59How is the autonomic nervous system regulated?Both sympathetic and parasympathetic nervous system are regulated by GPCR pathways
- 60Describe the structure of a classic GPCR?7 transmembrane domains, extracellular N (NH2) terminal, intracellular C (COOH) terminal. Ligand binding site in N terminal and between 2nd and 3rd transmembrane domains. G-protein coupling domain between C terminal and 3 intracellular loop.
- 61What is an alternative way in which GPCRs can be activated?N terminal can be cleaved by enzyme and enter ligand binding domain - self activation.
- 62What is the structure of G proteins? What from are they in when they are inactive? Where does GDP/GTP bind?1) Trimeric a,B,y subunits
2) GDP bound form
3) At the a subunit - 63What happens when a GPCR is activated?Conformational change triggers GDP switch to GTP, triggers dissociation of By subunit.
- 64Where are the effector molecules which the G protein act on?Near to membrane surface as a,B and y remain attached to membrane
- 65What is a G-protein?GTP-binding protein - has the ability to bind guanine nucelotides
- 66How many G-proteins can a GPCR activate? What limits this?Many until ligand dissociates from the GPCR.
- 67What does the 's' in Gs stand for? What does activation of a Gs GPCR lead to? Which subunit is involved?1) Stimulatory
2) Activates Adenyl Cyclase and Ca2+ channels
3) a - 68What does activation of the Gi receptor lead to? Which subunit is responsible?1) INhibit adenyl cyclase - a
2) Activate K+ channels - By - 69What does the activation of Gq lead to?Activates phospholipase C resulting in an increase in intracellular Ca2+
- 70Describe the general pathway of G-protein signalling1) First messenger (signal which activates GPCR)
2) First effectors - G proteins activate enzymes/channels
3) Second messengers - small molecules which can diffuse to reach their target
4) Second effectors - Often kinases also calmodulin - 71Give some examples of enzymesadenylyl cyclase, phospholipases, ion channels.
- 72Give examples of second messengers (4)1) cAMP
2) IP3 --- Ca2+
3) DAG
4) Diacylgylcerol - 73Describe the cascade when adrenaline acts on a B2R1) a subunit activates Adenyl Cyclase.
2) AC converts ATP to cAMP
3) cAMP activates PKA
4) PKA acts on target proteins - 74What effect does B2R activation have in the heart? In the lung? In the liver/striated muscle?1) Increased HR and contraction
2) Relaxation (smooth muscle)
3) Breaks down glucagon - 75What is the opposing pathway to AC?PDE - phosphodiesterases convert cAMP to AMP
- 76How is the level of cAMP regulated?Between production by ATP and breakdown by phosphodiesterases.
- 77Describe the structure of PKA? Where does cAMP bind?1) 2 catalytic domains and two regulatory domain.
2) Two molecules of cAMP bind to each regulatory unit - 78What does bind of cAMP trigger?Conformational change of PKA releasing the active catalytic domains which can then phosphorylate their targets
- 79What do kinases convert in order to phosphorylate their target? What else do kinases do?1) ATP (X3P) to ADP (X2)
2) Determines the localisation of the protein (ie near to where it needs to be to have an effect) or can create binding site for say adaptor molecules - 80What determines how long a protein is active for?Determined by when it is dephosphorylated by a phosphatase.
- 81What is a phosphate group? What molecules are converted by phosphatases?PO4^2-
H20 to HPO4^2- - 82Do phosphatases always inactivate proteins?no, roles of phosphatases and kinases can be reversed
- 83What do protein kinases act on?Phosphorylate specific amino acids
- 84Give 5 examples of serine/threonine kinases1) PKA (protein kinase A)
2) PKC (protein kinase C)
3) CaMK (Ca2+/Calmodulin-dependent kinase)
4) Raf (Rho Kinases, phosphorylase kinase)
5) ERK (extracellular signal regulated kinase) - 85Give 3 examples of tyrosine kinases1) JAK (Janus kinases)
2) FAK (focal adhesion kinases)
3) Receptor tyrosine kinases (growth factors such as PDGF, FGF, VEGF, NGF) - 86What partly determines the specificity of kinases binding to specific amino acid sequences?Whether the substrate and the kinase are colocalised
- 87What other preference for binding is shown by kinases?Preference for specific amino acid sequences
- 88What sequence does PKA prefer to bind to[R/K][R/K]X[S/T]
Arginine/Lysine residue downstream of Serine/Threonine
X=any amino acid - 89What sequence does PKC prefer to bind to[S/T]X[R/K]
X=any amino acid - 90What sequence does Tyrosine kinase prefer to bind to[R/K]X[D/E]X[Y]
Arginine/Lysine then Aspartate/Glutamate then Tyrosine
X=any amino acid - 91How does the activation of Gs lead to increased heart contractility?Activated PKA phosphorylates membrane L-type Ca2+ channels and Ryanodine receptors on the sarcoplasmic reticulum. There is then more Ca2+ available for each contraction increases the strength of the cell. PKA also increases relaxation of the heart by phosphorylation of Phospholamban. This removes phospholamban from SR Ca2+ ATPase (SERCA2A) disinhibiting it and allowing it to pump Ca2+ from the cytosol back into the SR. Increased and more rapid relaxation allows for greater volumes of blood. Troponin I is also phosphorylated by PKA decreasing its affinity for Ca2+ allowing for more Ca2+to be taken up into the SR
- 92What is inotropy?Contractility
- 93What is lusitropyrelaxation
- 94What causes positive inotropy?Increased Ca2+ entry by:
1) PKA phosphorylation of L-type Ca2+ channel
2) PKA phosphorylation of RyR - 95What causes positive lusitropy (ie more rapid relaxation)?Increased rate of Ca2+ removal:
1) PKA phosphorylation of PLB (SERCA2)
2) PKA phosphorylation of TNI (decreases affinity for Ca2+) - 96Talk through thisX
- 97Why does B1 stimulation in cardiac muscle cause contraction and B2 stimulation cause relaxation in smooth muscle even though both lead to activation of PKA?Different protein repatoire
- 98What protein isn't found in the lung? What is the PKA target in the lung?1) Troponin I
2) Myosin light chain kinase - 99What normally happens to cause contraction in smooth muscle in the lung?1) Ca2+ binds to calmodulin changing its conformation.
2) Activated calmodulin activates myosin light chain kinase (MLCK)
3) MLCK phosphorylates myosin light chain (MLC) leading to contraction - 100How does activation of B2 receptors on lunch smooth muscle cause relaxation?Pathway leads to activation of PKA. PKA phosphorylates MLCK. Phosphorylated MLCK has reduced affinity for myosin light chain. Reduces the amount of phosphorylated myosin light chain reducing contraction.
- 101What is the only organ which can release glucose into the bloodstream? What is the point of this?The liver - glucose can be taken up by muscle cells to generate ATP supporting contraction.
- 102In what two ways does PKA affect metabolism?1) Increases glycogen break down
2) Increases gluconeogenesis - 103Explain the role of PKA in metabolism1) PKA activates phosphorylase kinase
2) Phosphorylase kinase phosphorylates phosphorylase which leads to glycogen breakdown (Glycogen to to glucose-1-phosphate) - 104How does PKA regulate metabolism in terms of gene expression1) PKA can activate transcription factors such as CREB
2) Phosphorylated CREB stimulates transcription of genes which code for enzymes which regulate metabolism. CREB binds to CRE binding region of DNA increasing gluconeogenesis in the liver - 105What happens as you travel down the cascade of Gs activation in the liver? Why?Amplification of the pathway from 1 molecule to 10^8 - at each step many molecules are activated, for example as long as the ligand is bound the GPCR can activate many G-proteins.
- 106—X
- 107—X
- 108What does CRE stand for?Cyclic AMP response element
- 109What other signalling hormones act via cAMPAdrenocorticotropic hormone
Adrenaline
Glucagon
Luteinizing Hormone
Parathormone
Thyroid Stimulating hormone
Vasopressin - 110Which tissues does: 1) Adrenocorticotropic hormone act on?Adrenal cortex, fat
- 111AdrenalineMuscle
Fat
Heart - 112GlucagonLiver
Fat - 113Luteinizing hormoneOvaries
- 114ParathormoneBone
- 115Thyroid stimulating hormoneThyroid
- 116Vasopressin?Kidney
Information
- Description
- Year 2 Developmental and Cellular Physiology of the Specialised Cell (Structure and Function of Ion Channels ) Flashcards on Introduction Into Cell Signalling, created by Anna Hogarth on 31/03/2016.
- Created by
- Anna Hogarth
- Views
- 1
- Tags
- Rating