Second messengers

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What is the substrate for nitric oxide synthase
L-arginine
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What is the second messenger associated with Gs GPCRS
increase cAMP production
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What is the second messenger activity asociated with Gq/11 GPCRS
increased IP3 and DAG production by PLCBeta
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What is the second messenger activity associated with Gi receptors
decreased cAMP production by adenylate cycalse
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The three types of kinase
Ser/thre kinases, receptor ser/thre. Dual specificy protein kinases, receptr tyrosine kinases, nonreceptor tyrosine kinase.
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What does BDNF do?
Sensitises pain pathways. It's upregulated in inflammation
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Where is BDNF synthesised
in primary sensory neurons and transported to their central terminals
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How does it alter pain processing?
through altered gene expression, NMDA receptor activation and trafficking.
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What kind of receptor does BDNF signal through
TrkB receptors.
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What happens when the BDNF binds
the two inactive monomers dimerize and phosphorylate
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What couples to active BDNF receptors
GRB2 (GPCR binding protein 2) and Sos (Son of sevenless, a guanine nucleotide exchange factor)
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What does the trk-B/GRB2/SOS complex do?
Activates Ras, a small GTPase which becomes active when bound to GTP
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What does Ras do?
Activates a MAP kinase cascade. resulting in active MAP kinase, which translocates to the nucleus to activate transcription factor
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How is the signal amplified?
Increasing the number of active signalling molecules at each stage in a cascade.
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What is one effect of local [cAMP]
Influence on memory formation, via pKA and CREB phosphorylation.
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How many isoforms of adenyl cyclase are there in the CNS
Eight
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What is common to all of them
they are all activated by Gas, all inhibited by Gai, and they all have TM domains bound to the membrane
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What is different about I, III and VIII
they are activated by calcium, calmodulin.
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What is different about V and VI
Inhibited by calcium
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What mediates the effect of cAMP
cAMP dependant PKA, which can phosphorylate ion channels, enzymes, transcription factors
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What's an AKAP
An A-kinase anchoring protein.
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What do AKAPs do?
use scaffold proteisn to restrict secondary messenger production to subcellular regions to maintain specificty of effects. Bind other signalling molecules to inegrate different signal pathways.
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Another way that spatio-temporal localisation is maintained
The physical properties of second messengers restrict signalling to specific regions, eg DAG in the membrane
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Example of processes calcium ions regulate
memory formation, vesicluar trafficking, neurogenesis,
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Most target proteins don't mind Ca2+ directly. How does it work?
They execute their effects by calmodulin
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The two types of ca2+ calmodulin dependant protein kinases
specialised and multifunctional
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What does sustained increased [Ca2+] cause
apoptotic/necrotic cell death by excitotoxicty. due to increased glutamate and NMDA receptor or decreased cytoplasic ca2+ buffering.
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What is the effect of global elevated Ca2+.
activates proteases, phospholipases and endonucleases, damaging the cytoskeleton, cell membranes and DNA.
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How does the cell regulate [Ca2+]i
storage in the er, enters by SERCA ATPase. leaves by various channels
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What is the second messenger associated with Gs GPCRS

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increase cAMP production

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What is the second messenger activity asociated with Gq/11 GPCRS

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What is the second messenger activity associated with Gi receptors

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The three types of kinase

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