PI3K synthesizes PIP3 downstream of ALK mutants

Stable Identifier
Reaction [transition]
Homo sapiens
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PI3K phosphorylates PIP2 to PIP3 downstream of activated ALK fusions and mutants, leading to activation of the AKT pathway as assessed by S473 phosphorylation (Bai et al, 2000; Slupianek et al, 2001; Slupianek et al, 2004; Chen et al, 2008). AKT signaling contributes to apoptotic escape and cellular proliferation through regulation of proteins such as CDKN1B/p27, CCND2 and BCL2L11/BIM, among others (Gu et al, 2004; Rassidakis et al, 2005; Marzec et al, 2007; reviewed in Chiarle et al, 2008; Hallberg and Palmer, 2013).

Literature References
PubMed ID Title Journal Year
11110708 Nucleophosmin-anaplastic lymphoma kinase associated with anaplastic large-cell lymphoma activates the phosphatidylinositol 3-kinase/Akt antiapoptotic signaling pathway

Ouyang, T, Morris, SW, Bai, RY, Duyster, J, Miething, C, Peschel, C

Blood 2000
18097461 The anaplastic lymphoma kinase in the pathogenesis of cancer

Chiarle, R, Piva, R, Ambrogio, C, Inghirami, G, Voena, C

Nat. Rev. Cancer 2008
15374880 Inhibition of Akt increases p27Kip1 levels and induces cell cycle arrest in anaplastic large cell lymphoma

Grammatikakis, I, Claret, FX, Amin, HM, Atwell, C, Rassidakis, GZ, Feretzaki, M, Medeiros, LJ, Lai, R, Lin, Q

Blood 2005
14962911 NPM-ALK fusion kinase of anaplastic large-cell lymphoma regulates survival and proliferative signaling through modulation of FOXO3a

Griffin, JD, Scheijen, B, Gu, TL, Gilliland, DG, Sternberg, DW, Tothova, Z

Blood 2004
11280786 Role of phosphatidylinositol 3-kinase-Akt pathway in nucleophosmin/anaplastic lymphoma kinase-mediated lymphomagenesis

Morrione, A, Xue, L, Hoser, G, Wasik, MA, Slupianek, A, Nieborowska-Skorska, M, Morris, SW, Majewski, M, Skorski, T

Cancer Res 2001
17353907 Oncogenic tyrosine kinase NPM/ALK induces activation of the rapamycin-sensitive mTOR signaling pathway

Bucki, R, Raghunath, PN, El-Salem, M, Halasa, K, Liu, X, Wlodarski, P, Kasprzycka, M, Marzec, M, Wasik, MA

Oncogene 2007
24060861 Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology

Palmer, RH, Hallberg, B

Nat. Rev. Cancer 2013
18923524 Oncogenic mutations of ALK kinase in neuroblastoma

Ohira, M, Kikuchi, A, Soda, M, Kato, M, Choi, YL, Nakagawara, A, Hayashi, Y, Wang, L, Ogawa, S, Chen, Y, Sanada, M, Takita, J, Mano, H, Igarashi, T

Nature 2008
15588951 NPM/ALK downregulates p27Kip1 in a PI-3K-dependent manner

Skorski, T, Slupianek, A

Exp. Hematol. 2004
Catalyst Activity

phosphatidylinositol-4,5-bisphosphate 3-kinase activity of PI3K-binding ALK fusions:PI3K [cytosol]

Normal reaction
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Cross References
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