Bio 1-L12- Signalling Through G protein coupled receptors

important classes of molecules involved in signal transduction pathways- 7

1. signalling molecules- ligands/hormones

2. receptors

3. g proteins

4. effector eznymes- adenylate

5. secondary messengers- CAMPS

6. protein kinases- pKA

7. phosphatase

G proteins structure

• G proteins- 3 subunits- alphabet gamma

• alpha- binds GTP/GDP- activate

• proteins- nucleotide exchange NEFS- open nucleotide binding and replace with GTP

  • beta gamma dissociate after

beta adrenergic receptor signalling pathway

1. ligand binds to beta adnregenic receptor- which activates G protein

2. alpha subunit disengages which binds to adenylate cyclase

3. adenylate cyclase converts ATP to cAMP(secondary messenger)

4. cAMP activates protein kinase A- which releases catalytic part

5. pKA phosphorylates hundreds of other proteins

termination of beta adrengenic

1. intrinsic GTPase- reset themselves

2. hormone dissociation- no more epinephrine- inactivated

3. receptor phosphorylation- recruits arresting which prevents interaction with G proteins

what can G proteins coupled receptors also do?

they can activate phosphoinosidtide cascade

steps of the phosphoinositide cascade

1. ligand binds to G protein coupled receptor- and activates alpha subunit- activates phospholipase C-PLC

2. PLC cleaves PIP2- and gives IP3(secondary) and DAG

3. IP3- diffuses and opens CA2+ channels in ER

4. Ca2+ diffuses in cytosol- rise in this recruits protein kinase C(PKa) into membrane

5. PKC activated by membrane bound DAG

6. PKC phosphorylates enzymes

how is phosphoinositide signal terminated?

• IP3 is metabolised to inositol- can’t open Ca2+ channels

• DAG is phosphorylated to phosphatide or hydrolysed to glycerol and fatty acids

what do calcium ions do?

bind to proteins and induces conformational changes

• bind to negative charge oxygen- cross link to segments

• also binds tightly to proteins and changes confirmation

• activates CALMODULIN- calcium sensor

what do calmodulin do in relation to calcium ions?

• calmodulin is a calcium sensor

• when levels of calcium at over 500nM it exposes the hydrophobic surfaces

• calmodulin activates target proteins such as calmodulin dependent protein kinases