signal transduction

• transduction 


  cascades of molecular interactions relay signals from receptors to target molecules in cell
• signal transmission can be cascade of protein phosphorylation
• protein kinases transfer phosphates from ATP to protein
• dephosphorylation 


  protein phosphatases remove phosphate from proteins

  molecular switch
• second messengers are inside cell

  • are small, nonprotein, water soluble
  • initiated by GPCRs and RTKs
  • e.g. cyclic AMP and calcium ions
• cAMP

  • adenylyl cyclase converts ATP to cAMP
  • broken down by phosphodiesterase to form AMP
• cAMP usually activates 


  protein kinase A
• cholera affects G protein involved in regulating salt and water excretion, as it forms biofilm and produces enzyme that acts as a toxin
• toxin from cholera

  • alters G protein, unable to hydrolyse GTP to GDP
  • switch is on all the time
  • leads to activation of adenylyl cyclase and therefore cAMP
  • causes dramatic efflux of Cl- ions and water
  • leads to watery diarrhoea
• calcium ions and inositol triphosphate

  • acts a second messenger
  • normal conditions-intracellular calcium concentration is very low
• calcium release involves 


  IP3 and DAG as additional second messengers
• IP3 as second messenger

  labels

  A) IP3

  B) G protein coupled receptor

  
• calmodulin

  • 4 calcium ion binding sites
  • induces conformational changes to bind to other proteins
  • phosphates and kinases often regulated
  • adenylyl cyclase's and phosphodiesterase
• signalling can

  • regulation of gene expression
  • activity of enzyme
  • behaviour of cell
• response fine tuning

  • amplifying signal
  • specificity of response
  • overall efficiency, scaffolding proteins enhance
  • termination of signal
• scaffolding proteins

  • large relay proteins other relay proteins are attached to
  • increase signal transduction
• termination of signal

  • ligand concentration falls, fewer receptors bound
  • unbound receptors revert to inactive site