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 Rodriguez-Viciana, P, Warne, PH, Dhand, R, Vanhaesebroeck, B, Gout, I, Fry, MJ, Waterfield, MD, Downward, J	Nature	1994
24897931	PI3K/AKT signaling pathway and cancer: an updated review Martini, M, De Santis, MC, Braccini, L, Gulluni, F, Hirsch, E	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 Gysin, S, Salt, M, Young, A, McCormick, F	Genes Cancer	2011
1716764	Association of p21ras with phosphatidylinositol 3-kinase Sjölander, A, Yamamoto, K, Huber, BE, Lapetina, EG	Proc. Natl. Acad. Sci. U.S.A.	1991
21779497	RAS Interaction with PI3K: More Than Just Another Effector Pathway Castellano, E, Downward, J	Genes Cancer	2011
26085527	The Key Role of Calmodulin in KRAS-Driven Adenocarcinomas Nussinov, R, Muratcioglu, S, Tsai, CJ, Jang, H, Gursoy, A, Keskin, O	Mol. Cancer Res.	2015
31135801	The structural basis for Ras activation of PI3Kα lipid kinase Zhang, M, Jang, H, Nussinov, R	Phys Chem Chem Phys	2019
17998941	Oncogenic signaling of class I PI3K isoforms Denley, A, Kang, S, Karst, U, Vogt, PK	Oncogene	2008
8665852	Activation of phosphoinositide 3-kinase by interaction with Ras and by point mutation Rodriguez-Viciana, P, Warne, PH, Vanhaesebroeck, B, Waterfield, MD, Downward, J	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 Pacold, ME, Suire, S, Perisic, O, Lara-Gonzalez, S, Davis, CT, Walker, EH, Hawkins, PT, Stephens, L, Eccleston, JF, Williams, RL	Cell	2000