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28 Cards in this Set
- Front
- Back
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describe the steps in a generalised signalling pathway
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1) production of signalling molecule 2)release y exocytosis 3) transport to target cell 4)binding and activation of receptor 5)signal transduction pathways 6)a) short term changes in cellular function, metabolism or movement b)long term changes in gene expression 7)a) termination by receptor inhibition OR removal of extracellular signal |
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Describe 3 properties a good signal must have
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It must be specific to a defined signal small enough to diffuse rapidly through the cytosol or across membranes Made, mobilised or altered quickly- response is rapidly switched on or off |
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describe, using an example, how signals can be amplified
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the more steps in a cascade, the greater the signal amplification as each molecule produces/activates many more as the sequence goes on; One molecule of epinephrine to binding a GPCR induces the synthesis of a large number of cAMP molecules which activate PKA, each of which can phosphorylate many product molecules. |
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Which signalling pathways are fast and slow to take effect?
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those which end in alteration of protein function are fast to take effect (< 1 second - 1 minute)whilst those which end in the alteration of protein synthesis are slower (minutes to hours)
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describe how a signal might be terminated
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receptor and signalling molecule sequestration into endosomes down-regulation receptor or signalling protein inactivation production of inhibitory proteins |
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Outline the differences between autocrine, paracrine and endocrine signalling, giving examples of each.
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autocrine- cells respond to signals they themselves have produced- growth factors such as interleukin 6 and vascular endothelial growth factor paracrine- signalling molecules released by cell only affect target cells in close proximity- release of ACh at NM junction endocrine- signalling molecules are produced and secreted into the bloodstream to affect DISTANT target cells- hormones! |
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What are some of the human endocrine glands?
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Pituitary (brain), pineal, parathyroid, thyroid, thymus, adrenal, testis, ovaries.
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Name and describe the three families of hormones
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Peptides/proteins- majority of hormones. Hydrophilic and lipophobic- bind to cell surface receptors. Precursors are preprohormones- cleaved to prohormones then hormones. Stored in vesicles until needed. Amines- derived from aa tyrosine. two families- catecholamines (hydrophilic and lipophobic- extracellular binding) and thyroid hormones (hydrophobic and lipophilic- bind intracellularly) Steroids- lipids derived from cholesterol. not stored after formation, but diffuse freely into the bloodstream (usually with a carrier molecule) lipophilic- intracellular binding. |
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Where does the cholesterol for making steroid hormones come from?
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From low density lipoproteins which have been internalised via receptor mediated endocytosis, then a series of enzymatic reactions are carried out.
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Which of the two major cellular responses does signalling from a GPCR usually initiate? approximately how many GPCRs are encoded by the human genome?
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a change in activity of pre existing proteins. Around 900!
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Where are GPCRs commonly found? do they all have short term effects?
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In the olfactory and gustatory systems, they mainly have short term effects, but can have long term ones occasionally
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What are the three main subunits in a GPCR pathway?
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A recpetor A coupled trimeric G protein The effector protein |
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Describe the typical receptor in a GPCR system
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A protein with seven a-helical transmembrane protein regions (H1-H7), 4 extracellular segments connecting them on the outside (E1-E4) and 4 intracellular segments connecting them on the inside (C1-C4)
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Which segment of the GPCR receptor generally interact with the G protein?
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C3 and C4
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Describe the typical G protein coupled to a receptor
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A trimeric set of proteins - G alpha, Beta and Gamma. G a can bind to GDP/GTP. G gamma is not directly bound to the membrane. |
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Describe how the effector is activated in the GPCR pathway
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hormone binds to the receptor causing a conformational change- activated receptor binds the G a subunit. Binding causes G a to dissociate from GDP and GTP binds in its place- causing G a to dissociate from the receptor and G b and g. Ga activates the effector as the hormone dissociates from the receptor. GTP on G a is hydrolysed to GDP and the initial arrangement is resumed. |
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What are second messengers?
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Small intracellular signalling molecules whose concentration is often changed by binding of ligands to receptors (including GPCRs). They can facilitate amplification of an extracellular signal.
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Give some examples of second messengers and what they do
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cAMP- activates protein kinase A cGMP- activates protein kinase G DAG- activates PKC IP3 (inositol triphosphate) opens ER Ca2+ channels Ca2+ and membrane bound phosphatidyl inositol derivatives |
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What are used as effector proteins in the cAMP dependent pathway and what do they do? How are they activated or inhibited?
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Adenylyl cyclase- synthesises cAMP. They can be activated or inhibited by opposing GPCR systems- G alpha s and G alpha I coupled receptors.
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Describe the shape of PKA and how binding initiates phosphorylation. How many cAMP binding sites are there on PKA? How are R subunits joined?
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It has 4 subunits- 2 regulatory and 2 catalytic subunits. when cAMP binds to the R subunits, a conformational change take place and their affinity for the C subunits decreases. The complex dissociates and the C subunits are free to catalyse phosphorylation. Each R subunit can bind 2 cAMP (on sites CNB-A and CNB-B). they are joined by a flexible linker that has a docking domainfor AKAP. |
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Describe two ways in which down regulation can occur in the cAMP pathway |
The receptor has less affinity for its ligand when G as is GTP bound cAMP phosphodiesterase can hydrolase cAMP to 5'-AMP |
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What is feedback repression? Give an example |
Where a pathway end product blocks an earlier step. PKA in the cAMP pathway can phosphorylate and reduce the efficiency of the receptor |
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Give an example of a cAMP-PKA pathway. In addition to the generic pathway, what does cAMP degradation result in in this pathway? |
The mechanism of action of AVP, an antidiuretic hormone, on the kidney cortical collecting tubule. After cAMP degradation, the activated C subunit translocates into the nucleus where it causes a change in gene expression. |
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When a GPCR effector protein is phospholipase, which two second messengers are produced when it is activated and how? |
Phospholipase can hydrolyse the membrane phospholipid phosphatidylinositol to give IP3 and DAG |
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Describe the IP3 pathway in 8 steps |
1) ligand binds to GPCR and activates PLC via Ga 2) PLC cleaves PIP2 to DAG and IP3 3)IP3 opens channels in the ER membrane 4) Ca2+ is released into the cytosol 5)PKC is recruited to the plasma membrane 6)DAG activates PKC 7)PKC can phosphorylate 8)a protein associated with IP3-gated Ca2+ channels binds to and opens plasma membrane Ca2+ channels |
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What two domains do all steroid hormone receptors have? |
A hormone binding domain at the COOH end and a DNA bonding domain. |
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Describe the DNA binding domain of steroid hormone receptors |
It has many cysteine residues and cys-2x-cys motifs which can be bridged by Zn to form 'zinc fingers' that can enhance DNA transcription |
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What does aldosterone do in the kidney? Where is it released from? |
It stimulates reabsorbtion in the distal region of the tubule. It is released by the adrenal gland. |
