G protein coupled receptors have an extracellular binding site to which the hormone binds and an intracellular cytoplasmic tail region to which G-proteins may bind.
G proteins act as a switch and functionally couple the receptor to their target enzymes or ion channels. Switch means there is an inactive state when the hormone is not bound to the receptor and when the hormone binds, there is activation. G-proteins or heterotrimeric GTP binding proteins is a set of 3 proteins, G alpha, G beta and G- gamma which are present as an inactive complex bound to membrane just near the hormone receptor.
The alpha subunit of G proteins is bound to GDP in inactive state.When the hormone binds to its receptor, receptor interacts with the G proteins and GDP bound to alpha subunit is replaced by GTP, which is now said to be in active state. This replacement of GDP with GTP causes alpha subunit to dissociate from beta and gamma subunits and move and associate with some other proteins causing either opening/closing of ion channels or they affect the activity of enzymes like adenyl cyclase and phospholipase C.
G proteins which stimulate adenyl cyclase activity are known as G stimulatory proteins i.e Galpha s. while that which inhibits their activity ate known as inhibitory G proteins i.e Galphai. The G proteins which affect the activity of phospholipase C are known as G q proteins. The effect of the hormone on the cell depends on the type of the receptor it binds for e.g. same hormone in one cell may have a receptor which is linked to stimulatory G proteins while in other cells it may have a receptor which is linked to inhibitory G proteins. By the change in the activity of these enzymes, second messenger systems or we can say signalling pathways are activated.
Adenylcyclase-cAMP pathway
When adenyl cyclase enzyme is activated, it causes the conversion of ATP to cAMP. cAMP in turn cause the activation of cAMP dependent protein kinase A which causes phosphorylation of some proteins/enzymes in the cell. Now these proteins may be involved in biological reactions or these phosphorylated protein inturn activate or inhibit other proteins which are involved in cellular reactions. So ultimately this process affects the function of the cells. In addition,PKA can also increase/decrease the transcription of some genes.Close to these genes, is present a region known as cAMP-responsive element (CRE) region of DNA. A subunit of PKA moves to the nucleus and phosphorylates another protein, the cAMP-responsive element binding protein (i,e CREB protein) which then binds to CRE and alters transcription of the genes where CRE is present. The set of proteins activated by cAMP varies in different cells. So adenyl cyclase activation in different cells leads to different actions. However if same adenyl cyclase is activated by different ligands in the same cell, it leads to same actions. So in this pathway, cAMP acts as a second messenger.
Phospholipase C-IP3-DAG-Calmodulin pathway
When phospholipase C is activated by Gq proteins, it causes breakdown of the membrane phospholipid phosphatidylinositol 4,5 bi or di phosphate (PIP2) into IP3, i.e inositol triphosphate and Diacyl glycerol (DAG). Ip3 acts on IP3 receptor (IP3R) present on endoplasmic reticulum. This IP3R is itself a ligand gated calcium channel. When IP3 binds, it opens up causing release of calcium ions from ER into the cytososl. The calcium ions in turn bind with calmodulin causing activation/inhibition of calmodulin dependent protein kinases.
DAG activates protein kinase C which then phosphorylates other proteins just as we saw for adenyl cyclase dependent kinases. So in this case IP3, DAG and calcium are second messengers.
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