• 1 Function
• 2 Examples of GPCR partners
• 3 Genes
• 4 See also
• 5 References
• 6 External links  "   
  

• 3 IP₃ Signaling Pathway
• 4 Function
  • 4.1 Human
    

3. IP₃ Signaling Pathway

PLC cleavage of PIP₂ to IP₃ and DAG initiates intracellular calcium release and PKC activation.   
(Click on the nested screen symbol on the lower left to enlarge the diagram.)     
 

    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.^[10]

    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.^[11]

    IP₃ (also abbreviated Ins3P) 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, IP₃ is able to bind to the Ins3P receptor (Ins3PR) on a ligand-gated Ca²⁺ channel that is found on the surface of the ER. The binding of IP3 (the ligand in this case) to InsP3R triggers the opening of the Ca²⁺ channel, and thus release of Ca²⁺ into the cytoplasm.^[11] 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.^[10]

4. Function

    4.1 Human

    IP₃'s main functions are to mobilize Ca²⁺ from storage organelles and to regulate cell proliferation and other cellular reactions that require free calcium. (In smooth muscle cells, for example, an increase in concentration of cytoplasmic Ca²⁺ results in the contraction of the muscle cell).^[12]

    In the nervous system, IP₃ serves as a second messenger, with the cerebellum containing the highest concentration of IP₃ receptors.^[13] There is evidence that IP₃ receptors play an important role in the induction of plasticity in cerebellar Purkinje cells.^[14]

Vesicle fusion may depend on SNARE proteins in the presence of increased intracellular calcium (Ca²⁺) concentration.