BLOCK-iT™ RNAi Express

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PI3K/AKT Pathway

The Phosphatidylinositol 3-kinase (PI3K) and AKT (Protein kinase B) signaling pathway regulates many different cellular processes including cell proliferation, survival, migration, glucose metabolism, and angiogenesis. The dysregulated activation of the PI3K/AKT signaling pathway has also been demonstrated in a variety of different human cancers.

PI3Ks are heterodimeric proteins that catalyze the phosphorylation of membrane associated phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to phosphatidylinositol-3,4,5-triphosphate [PI(3,4,5)P3] in response to growth factor receptor activation. AKT kinases and 3-phosphoinositide-dependent kinase-1 (PDK1) bind to PI(3,4,5)P3 and are recruited to sites of PI3K activation. PDK1 subsequently activates AKT kinase by phosphorylation of the kinase domain. In response to activation, AKT kinases phosphorylate many different target proteins including key regulators of cellular survival such as Bad, caspase-9, IκB kinase, and forkhead transcription factors. AKT activity is further regulated through binding to various interacting proteins and is attenuated by protein phosphatases and the PI(3,4,5)P3 lipid phosphatases PTEN and SHIP.
PI3K/AKT Pathway Validated Stealth RNAi™ siRNA
AKT/ Protein Kinase B
Phosphoinositide 3-kinase (PI3K)
PIP3 phosphatases
Targets of AKT
AKT interaction proteins


1. Cantley, L.C. The Phosphoinositide 3-kinase pathway. Science 296, 1655-1657 (2002).
2. Chang, F. et al. Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy. Leukemia 17, 590-603 (2003).
3. Franke, T.F. PI3K/Akt and apoptosis: size matters. Oncogene 22, 8983-8998 (2003).
4. Luo, J., Manning, B.D., & Cantley, L.C. Targeting the PI3K-AKT pathway in human cancer: Rationale and promise. Cancer Cell 4, 257-262 (2003).
5. Vivanco, I. & Sawyers, C.L. The phosphatidylinositol 3-kinase-AKT pathway in human cancer. Nat. Rev. Cancer 2, 489-501 (2002).