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==Signaling pathway== [[Image:PIP2 cleavage to IP3 and DAG.jpg|thumb|PLC cleavage of PIP<sub>2</sub> to IP<sub>3</sub> and DAG initiates intracellular calcium release and PKC activation.]] Increases in the intracellular Ca<sup>2+</sup> concentrations are often a result of IP<sub>3</sub> activation. When a [[ligand]] binds to a [[G protein-coupled receptor]] (GPCR) that is coupled to a Gq [[heterotrimeric G protein]], the Ξ±-subunit of Gq can bind to and induce activity in the PLC [[isozyme]] PLC-Ξ², which results in the cleavage of PIP<sub>2</sub> into IP<sub>3</sub> and DAG.<ref name="Biaggioni">Biaggioni I., Robertson D. (2011). Chapter 9. Adrenoceptor Agonists & Sympathomimetic Drugs. In: B.G. Katzung, S.B. Masters, A.J. Trevor (Eds), Basic & Clinical Pharmacology, 11e. Retrieved October 11, 2011 from {{cite web |url=http://www.accessmedicine.com/content.aspx?aID=4520412 |title=AccessMedicine | Case Study |access-date=2011-11-30 |url-status=dead |archive-url=https://web.archive.org/web/20110930100935/http://www.accessmedicine.com/content.aspx?aID=4520412 |archive-date=2011-09-30 }}.</ref> If a [[receptor tyrosine kinase]] (RTK) is involved in activating the pathway, the isozyme PLC-Ξ³ has [[tyrosine]] residues that can become phosphorylated upon activation of an RTK, and this will activate PLC-Ξ³ and allow it to cleave PIP<sub>2</sub> into DAG and IP<sub>3</sub>. 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.<ref name="Barrett">Barrett KE, Barman SM, Boitano S, Brooks H. Chapter 2. Overview of Cellular Physiology in Medical Physiology. In: K.E. Barrett, S.M. Barman, S. Boitano, H. Brooks (Eds), Ganong's Review of Medical Physiology, 23e. {{cite web|url=http://www.accessmedicine.com/content.aspx?aID%3D5243085 |title=AccessMedicine | Objectives |access-date=2011-11-30 |url-status=dead |archive-url=https://web.archive.org/web/20120614133549/https://www.accessmedicine.com/content.aspx?aID=5243085 |archive-date=2012-06-14 }}. </ref> IP<sub>3</sub> (also abbreviated Ins(1,4,5)P<sub>3</sub> 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 it has been produced by the action of PLC. Once at the ER, IP<sub>3</sub> is able to bind to the Ins(1,4,5)P<sub>3</sub> receptor Ins(1,4,5)P<sub>3</sub>R which is a ligand-gated Ca<sup>2+</sup> channel that is found on the surface of the ER. The binding of IP<sub>3</sub> (the ligand in this case) to Ins(1,4,5)P<sub>3</sub>R triggers the opening of the Ca<sup>2+</sup> channel, and thus release of Ca<sup>2+</sup> into the cytoplasm.<ref name= "Barrett"/> In heart muscle cells this increase in Ca<sup>2+</sup> activates the [[ryanodine receptor]]-operated channel on the SR, results in further increases in Ca<sup>2+</sup> through a process known as calcium-induced calcium release. IP<sub>3</sub> may also activate Ca<sup>2+</sup> channels on the cell membrane indirectly, by increasing the intracellular Ca<sup>2+</sup> concentration.<ref name = "Biaggioni"/>
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