RAS:GTP binds PI3K

Stable Identifier
Reaction [binding]
Homo sapiens
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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
24897931 PI3K/AKT signaling pathway and cancer: an updated review

Martini, M, De Santis, MC, Braccini, L, Gulluni, F, Hirsch, E

Ann. Med. 2014
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
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
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