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bio 124 Lecture 3
Signal Transduction
26
Biology
Undergraduate 1
02/23/2013

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Term
where are second messengers found?
Definition

inside of a cell.

 

 

Term
what are the benefits of multistep pathways?
Definition

multistep pathways can amplify a signal so a few molecules can produce a large cellular response.

they also provide more opportunities for coordination and regulation of cellular responses

Term
in many pathways how is a signal transmitted?
Definition

through a cascade of protein phosphorylation

 

protein kinases transfer phosphates from ATP to protein, a process called phosphorylation. this occurs most commonly on serine, threonine (or tyrosine) residues

Term
which enzyme removes phosphates from proteins in a process called dephosphorylation?
Definition

protein phosphotases

 

dephosphorylation = protein deactivation

Term
the phosphorylation/dephosphorylation system acts a a molecular switch turning activities on, off or up and down as required. what is the activity of a particular pathway regulated by?
Definition
the ratio of kinase to phophatase activity within a cell
Term
second messengers are small ........... water soluble molecules or ..... that readily spread throughout a cell by ...........
Definition

nonprotein

ions

diffusion

Term

true or false?

second messengers participate in pathways initiated by GPCRs and RTKs

Definition

true.

 

Cyclic AMP and calcium ions are common second messengers

Term
name one of the most widely used second messengers
Definition

cyclic AMP (cAMP) 

 

adenylyl cyclase is an enzyme in the pm which converts ATP to cAMP in response to an extracellular signal

Term
which enzyme can break down cAMP?
Definition
phosphodiesterase breaks down cAMP to AMP which is inactive
Term
other components of cAMP pathways are G proteins, ........ and protein kinases
Definition

GPCRs

 

cAMP usually activates protein kinase A, which phosphorylates various other proteins.

Term

how do G proteins provide further regulation of cell metabolism in second messengers 

 

Definition
some inhibit adenylyl cyclase
Term
what is the causative agent of cholera?
Definition

toxin from bacterium vibrio cholerae.

 

the bacteria colonise the small intestine (forming a biofilm) and produce an enzyme that acts as a toxin

Term
what is the function of the G protein affected by vibrio cholorae?
Definition
involved in regulating salt and water excretion.
Term
cholera toxins activate a G protein. what is this G protein UNABLE to do?
Definition

hydrolyse GTP to GDP hence it is switched ON all the time.

consequence : constant activation of adenylate cyclase and contionous production of cAMP.

Term
which transmembrane regulator is activated from high cAMP levels in cholera?
Definition

CFTR cystic fibrosis transmembrance conductance regulator.

this causes dramatic EFFLUX of chloride ion and water from infected cells leading to watery diorrhoea.

Term
calcium ion act as .......... messengers in many pathways. calcium is an important 2nd messenger because cells can ............. its .............. under normal conditions intracellular calcium concentration is very ..........
Definition

second

regulate

concentration

low

 

at some concentration the intracellular level maybe 10,000 times lower than in the blood stream or plant cell wall

Term
pathways leading to the release of calcium ions involve additional second messengers. what are thery?
Definition

Inositol triphosphate - IP3

Diacylglycerol -DAG

 

cytoplasmic calcium is actively pumped into the ER/mitochondria/chloroplasts to keep cytoplasmic conc of calcium ions low.

Term
in the build up to the release of calcium a signalling molecule binds to a receptor activating which phospholipase?
Definition

phospholipase C

 

this then cleaves membrane phospholipid PIP2 into DAG and IP3

Term
how does IP3 get from the cytosol to the IP3 gated calcium chanel in the ER membrane causing it to open?
Definition

diffusion

 

calcium ions flow out down conc gradient causing cytoplasmic ca levels to rise. the calcium ions then activate the next protein in one (or more) signalling pathways

Term
what is Calmodulin? (CaM)
Definition

a very specific calcium modulated protein with 4 ca+ binding sites

 

ca+ binding induces conformational changes allowing CaM to bind to other proteins causing activation or deactivation

Term
proteins most often regulated by CaM are protein phosphatases and kinases but can you name two other molecules CaM also regulates?
Definition

the activity of adenyly cyclases and phosphodiesterases in cAMP formation/breakdown.

 

 

CaM also activates Ca2+ATPase which pumps Ca2+ out of cell to < Ca2+ concentration

Term
a signal transduction pathway leads to the regulation of one or more cellular activities. where may this response occur?
Definition

in the cytoplasm or the nucleus

 

many signalling pathways regulate enzyme/protein synthesis by turning genes on/off in the nucleus

Term
the final activated molecule in the signalling pathway may fuction as what?
Definition
a transcription factor (eg, Ras pathway)
Term
when fine-tuning a signal response what four things must we consider?
Definition
  • amplifying the signal thus the response
  • specifictiy of the response
  • overall efficiency of response, enhanced by scaffolding proteins
  • termination of signal
Term
what are scaffolding proteins?
Definition

they are large relay proteins to which other relay proteins are attacthed

 

these proteins can increase signal transduction efficiencey by grouping together different proteins invilved in the same pathway

Term
with regards to termination of the signal, if ligand concentration falls then fewer receptors will be bound. which state are the unbound receptors in? (active or inactive)
Definition

inactive.

 

other inactivation mechanisms include Ca2+ and CaM who contribute to a negative feedback loop to reduce cytoplasmic Ca2+ levels

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