intracellular signalling Flashcards
What are some types of intracellular signals?
- ions
- proteins
- dissolved gases
- second messengers
What are the two types of proteins used in signal transduction and where are they found?
- hydrophobic proteins (membrane-associated)
- hydrophilic proteins (cytosol)
What are the 3 ways signalling molecules are controlled?
- by post translational modification
- by regulating whether a G protein has bound (GDP or GTP)
- by provision of activators
What is kinase and what does it do?
- enzyme
- phosphorylates proteins
What is phosphatase and what does it do?
- enzyme
- dephosphorylates proteins
What are the 2 enzymes involved in protein phosphorylation?
- kinase (phosphorylates)
- phosphatase (dephosphorylates)
What are the two types of kinases?
- serine/threonine kinases
- tyrosine kinases (non receptor and receptor)
What are GEFs and what do they do?
- guanine exchange factors
- promote exchange of GDP for GTP
What is Ras? Why is it significant?
- a small GTPase
- Ras mutations found in a large proportion of adenocarcinomas
What are voltage gated Na+ channels composed of?
- alpha subunit
- 4 beta subunits
How do voltage gated Na+ channels stop other ions from getting through?
- too small for K+ ions to cross
- contains negatively charged amino acids to stop Cl- ions passing
What do the alpha subunits in voltage gated Na+ channels do?
- opens in response to a change in voltage
- contains 4 homologous domains that form the pore
What do the beta subunits in voltage gated Na+ channels do?
traffic the channel and regulate its kinetic properties
How do the alpha subunits detect voltage?
- 4 homologous domains have 6 transmembrane regions
- region 4 has AA with positive R-groups which sense the voltage
How does the nicotinic acetylcholine receptor work?
- 2 acetylcholine molecules bind the alpha subunits
- causes movement of the M2 helices (opens channel)
Describe the structure of the nicotinic acetylcholine receptor
- 5 subunits (2 alpha, beta, gramma, delta)
- transmembrane region M2 of each subunit forms channel
How are the effects of Ca2+ mediated?
- kinases (e.g CAM kinase)
- phosphatases (e.g Calcineurin)
What types of channels are Ca2+ channels?
ligand gated or voltage gated
What is the structure of a G-protein coupled receptor
- typically has 7 transmembrane domains
How does G-protein coupled receptor activation work?
- ligand binds to receptor, and affinity for G-protein increases (may already be coupled)
- receptor activation changes conformation of internal portion of receptor, releasing GDP
How does the GPCR initiation of signalling work
- GDP attached to alpha subunit is replaced by GTP
- alpha subunit and beta-gamma complex dissociate (can each initiate further signalling)
- GTP then hydrolysed to GDP and beta-gamma recombine with alpha subunit
What are the types of GTP-binding proteins?
- small GTPases
- heterotrimeric G proteins (in GPCR signalling)
How is GTP-binding protein activity regulated?
- guanine exchange factors (GEFs)
- intrinsic GTPase activity
- GTPase-activating proteins speed up hydrolysis of GTP
Which 3 subunits to G-proteins consist of?
alpha beta gamma
What are the steps happening the beta adrenergic receptor (relaxation of blood vessels in skeletal muscle)?
- GPCR
- GTP binds to G-alpha S on G protein
- adenylyl/andenylate cyclase converts ATP to cAMP
- cAMP activates PKA
How does cholera affect us?
- cholera toxins inhibit GTPase activity of subunit G-alpha S
- prolonged signalling causes water and Cl- to move out of the cells lining the intestine (cAMP activates the cystic fibrosis transmembrane conductance regulator CFTR)
- results in diarrhoea, severe dehydration and death
How does whopping cough come about?
- bordetella pertussis bacterium releases an active adenylyl cyclase domain
- pertussis toxin renders G-alpha i inactive (inhibitor for adenylyl cyclase)
- prolonged signal stimulates coughing
