IP3 Signalling Pathway
Increases in the intracellular Ca2+ concentrations are often a result of IP3 activation. When a ligand binds to a G protein-coupled receptor (GPCR) that is coupled to a Gq heterotrimeric G protein, the α-subunit of Gq can bind to and induce activity in the PLC isozyme PLC-β, which results in the cleavage of PIP2 into IP3 and DAG.
If a receptor tyrosine kinase (RTK) is involved in activating the pathway, the isozyme PLC-γ has tyrosine residues that can become phosphorylated upon activation of an RTK, and this will activate PLC-γ and allow it to cleave PIP2 into DAG and IP3. This occurs in cells that are capable of responding to growth factors such as insulin, because the growth factors are the ligands responsible for activating the RTK.
IP3 is a soluble molecule and is capable of diffusing through the cytoplasm to the ER, or the sarcoplasmic reticulum (SR) in the case of muscle cells, once produced by PLC. Once at the ER, IP3 is able to bind to a the Ins3PR receptor on a ligand-gated Ca2+ channel that is found on the surface of the ER. The binding of IP3 to InsP3R triggers the opening of the Ca2+ channel and the release of Ca2+ into the cytoplasm. In heart muscle cells this increase in Ca2+ activates the ryanodine receptor-operated channel on the SR, results in further increases in Ca2+ through a process known as calcium-induced calcium release. IP3 may also activate Ca2+ channels on the cell membrane indirectly by increasing the intracellular Ca2+ concentration.
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