Signal transduction mechanism for the DP2:

*(At first, it’s important to mention Prostaglandin D2 is considered as a ligand for 2

receptors: the first is DP1 and the second is DP2, and while DP 1 receptors are
coupled to Gαs proteins and signal through elevation of intracellular levels of cAMP,
the DP2 receptors on the other side are coupled to Gα i and their activation leads to
the elevation of intracellular calcium and reduction in cAMP.)

DP2 is a 7-transmembrane domain receptor linked with through a G protein to

phospholipase C. after receptor’s stimulation with Prostaglandin D2 triggers the G
protein replace the GDP with GTP that hydrolyze the latter into a GDP, causing the
Gi alpha subunit-linked heterotrimeric G proteins to break apart.

the Gi alpha subunits inhibit adenylyl cyclase who is responsible for converting AMP
into cAMP which will consequently result in down-regulating cyclic AMP-responsive
proteins who are supposed regularly to be involved in cell signalling. This decrease
in cAMP is thought to be responsible for contraction in smooth muscle.

meanwhile the G beta-gamma subunits have the ability to simulate phospholipase C

to dissociate the phosphatidylinositol triphosphate apart into both IP3 and DAG. the
first (IP3) is responsible for the regulation of Ca+2 cations signal pathways by raising
its levels depending on how much it is necessary, while the latter (DAG) is crucial for
the activation of certain protein kinase C enzymes that is responsible for
phosphorylation, thereby the regulation of the target proteins that are involved in cell
signalling.

The GRKs and the DAG-activated PKCs, phosphorylate DP2 receptor in order to
promote its internalization. while on the other side the arrestin-2 inhibits DP2 from
further activating heterotrimeric G proteins while also linking the DP2 to elements,
clathrin and clathrin adaptor AP2, of the receptor internalization machinery. These
pathways make the DP2 unable to mobilize heterotrimeric G proteins.