Reactome | RAS:GTP binds PI3K

RAS:GTP binds PI3K

Stable Identifier

R-HSA-9658253

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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GTP-bound RAS interacts with PI3K through a direct interaction with the 110 kDa catalytic subunit (Sjolander et al, 1991; Rodriguez-Viciana et al, 1994; Rodriguex-Viciana et al, 1996; Pacold et al, 2000; reviewed in Gysin et al, 2011; Castellano and Downward, 2011; Martini et al, 2014). Interaction with RAS stimulates the activity of PI3K by promoting a conformational change and/or mediating recruitment to the plasma membrane, among other possible mechanisms (Pacold et al, 2000; Denley et al, 2008; Zhang et al, 2019). The PI3K signaling pathway contributes to RAS-mediated cellular proliferation and survival and through RAC, contributes to cytoskeletal rearrangements and cell motility (reviewed in Vivanco and Sawyers, 2002; Castellano and Downward, 2011; Martini et al, 2014; Nussinov et al, 2015).

Literature References

PubMed ID	Title	Journal	Year
8052307	Phosphatidylinositol-3-OH kinase as a direct target of Ras Fry, MJ, Gout, I, Downward, J, Dhand, R, Waterfield, MD, Warne, PH, Rodriguez-Viciana, P, Vanhaesebroeck, B	Nature	1994
24897931	PI3K/AKT signaling pathway and cancer: an updated review De Santis, MC, Martini, M, Braccini, L, Hirsch, E, Gulluni, F	Ann. Med.	2014
12121613	Activation of phosphoinositide 3-kinase gamma by Ras Suire, S, Hawkins, P, Stephens, L	Curr. Biol.	2002
21779505	Therapeutic strategies for targeting ras proteins McCormick, F, Salt, M, Young, A, Gysin, S	Genes Cancer	2011
1716764	Association of p21ras with phosphatidylinositol 3-kinase Sjölander, A, Yamamoto, K, Lapetina, EG, Huber, BE	Proc. Natl. Acad. Sci. U.S.A.	1991
21779497	RAS Interaction with PI3K: More Than Just Another Effector Pathway Downward, J, Castellano, E	Genes Cancer	2011
26085527	The Key Role of Calmodulin in KRAS-Driven Adenocarcinomas Nussinov, R, Jang, H, Keskin, O, Tsai, CJ, Muratcioglu, S, Gursoy, A	Mol. Cancer Res.	2015
31135801	The structural basis for Ras activation of PI3Kα lipid kinase Nussinov, R, Zhang, M, Jang, H	Phys Chem Chem Phys	2019
17998941	Oncogenic signaling of class I PI3K isoforms Vogt, PK, Kang, S, Denley, A, Karst, U	Oncogene	2008
8665852	Activation of phosphoinositide 3-kinase by interaction with Ras and by point mutation Downward, J, Waterfield, MD, Warne, PH, Rodriguez-Viciana, P, Vanhaesebroeck, B	EMBO J.	1996
12094235	The phosphatidylinositol 3-Kinase AKT pathway in human cancer Vivanco, I, Sawyers, CL	Nat. Rev. Cancer	2002
11136978	Crystal structure and functional analysis of Ras binding to its effector phosphoinositide 3-kinase gamma Suire, S, Davis, CT, Walker, EH, Pacold, ME, Hawkins, PT, Stephens, L, Williams, RL, Lara-Gonzalez, S, Eccleston, JF, Perisic, O	Cell	2000