Reactome | PI3K-containing complexes phosphorylate PIP2 to PIP3

PI3K-containing complexes phosphorylate PIP2 to PIP3

Stable Identifier

R-HSA-109699

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, plasma membrane, endosome membrane

ReviewStatus

5/5

Locations in the PathwayBrowser

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Signal Transduction (Homo sapiens)

- Signaling by Receptor Tyrosine Kinases (Homo sapiens)
  - Signaling by Insulin receptor (Homo sapiens)
    - Insulin receptor signalling cascade (Homo sapiens)
      - IRS-mediated signalling (Homo sapiens)
        
        PI3K Cascade (Homo sapiens)
        
        PI3K-containing complexes phosphorylate PIP2 to PIP3 (Homo sapiens)
  - Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) (Homo sapiens)
    - IGF1R signaling cascade (Homo sapiens)
      - IRS-related events triggered by IGF1R (Homo sapiens)
        
        IRS-mediated signalling (Homo sapiens)
        
        PI3K Cascade (Homo sapiens)
        
        PI3K-containing complexes phosphorylate PIP2 to PIP3 (Homo sapiens)

General

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PI3K-containing complexes phosphorylate PIP2 to PIP3

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PI3K can be activated downstream of receptor tyrosine kinases (RTKs) such as insulin receptor IGF1R (Hadari et al. 1992, Kooijman et al. 1995). In unstimulated cells, PI3K class IA exists as an inactive heterodimer of a p85 regulatory subunit (encoded by PIK3R1, PIK3R2 or PIK3R3) and a p110 catalytic subunit (encoded by PIK3CA, PIK3CB or PIK3CD). Binding of the iSH2 domain of the p85 regulatory subunit to the ABD and C2 domains of the p110 catalytic subunit both stabilizes p110 and inhibits its catalytic activity. This inhibition is relieved when the SH2 domains of p85 bind phosphorylated tyrosines on activated RTKs or their adaptor proteins. Binding to membrane-associated receptors brings activated PI3K in proximity to its membrane-localized substrate, PIP2, facilitating phosphorylation (Mandelker et al. 2009, Burke et al. 2011; reviewed in Koyasu et al, 2003; Engelman et al, 2006).

Literature References

PubMed ID	Title	Journal	Year
7543144	Insulin-like growth factor induces phosphorylation of immunoreactive insulin receptor substrate and its association with phosphatidylinositol-3 kinase in human thymocytes Lauf, JJ, Kappers, AC, Rijkers, GT, Kooijman, R	J. Exp. Med.	1995
21827948	Dynamics of the phosphoinositide 3-kinase p110? interaction with p85? and membranes reveals aspects of regulation distinct from p110? Vadas, O, Burke, JE, Finegan, T, Williams, RL, Perisic, O, Berndt, A	Structure	2011
1381348	Insulin and insulinomimetic agents induce activation of phosphatidylinositol 3'-kinase upon its association with pp185 (IRS-1) in intact rat livers Rothenberg, P, Roberts, CT, LeRoith, D, Nadiv, O, Tzahar, E, Yarden, Y, Zick, Y, Hadari, YR	J. Biol. Chem.	1992
19805105	A frequent kinase domain mutation that changes the interaction between PI3Kalpha and the membrane Cheong, I, Mandelker, D, Zhu, J, Schmidt-Kittler, O, Kinzler, KW, Vogelstein, B, Amzel, LM, Gabelli, SB, Huang, CH	Proc. Natl. Acad. Sci. U.S.A.	2009
16847462	The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism Cantley, LC, Luo, J, Engelman, JA	Nat. Rev. Genet.	2006
12660731	The role of PI3K in immune cells Koyasu, S	Nat Immunol	2003