Requirement for the PI3K/Akt pathway in MEK1-mediated growth and prevention of apoptosis: identification of an Achilles heel in leukemia

Blalock, William L.; Navolanic, Patrick M.; Steelman, Linda S.; Shelton, John G.; Moye, Phillip W.; Lee, J T; Franklin, Richard A.; Mirza, Amer M.; McMahon, Martin; White, Martyn K.; McCubrey, James A.

doi:10.1038/sj.leu.2402925

Cited by 58 publications

(59 citation statements)

References 57 publications

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“…We have observed that inhibition of the Raf/MEK/ ERK and PI3K/PTEN/Akt/mTOR pathways is usually more effective in inducing apoptosis and synergy between inhibitions of both pathways is often observed. 133 This is often the case in drug-resistant leukemias, as the drug-resistant cells often display elevated signaling of both pathways.…”

Section: Combining Signal Transduction Inhibitorsmentioning

confidence: 99%

Targeting survival cascades induced by activation of Ras/Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways for effective leukemia therapy

et al. 2008

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Section: Combining Signal Transduction Inhibitorsmentioning

confidence: 99%

Targeting survival cascades induced by activation of Ras/Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways for effective leukemia therapy

et al. 2008

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“…82,83 Furthermore, Raf/MEK/ERK and PI3K/AKT pathways can synergize to induce cell survival and cellular transformation, 84 and the activation of PI3K contributes for MEK1-responsive growth and survival. 85 We therefore proposed that the apoptotic effects of PI3K/AKT inhibitor could be enhanced by cotreatment with MEK inhibitor. Indeed, the combination of the MAPK inhibitor PD98059 with LY294002 dramatically decreased cell growth and increased apoptosis in two different cell lines studied.…”

Section: Figure 10mentioning

confidence: 99%

Inhibition of phosphatidylinositol 3-kinase dephosphorylates BAD and promotes apoptosis in myeloid leukemias

et al. 2003

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“…[16][17][18] Activated ERK1 and ERK2 serine (S)/T kinases phosphorylate and activate a variety of substrates. [19][20][21][22][23][24][25] 90 kDa ribosomal six kinase 1 (p90 Rsk1 ) is one such substrate. p90 Rsk1 can activate the cyclic-AMP response element-binding protein (CREB) transcription factor.…”

Section: Overview Of the Ras/raf/mek/erk Pathwaymentioning

confidence: 99%

Contributions of the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to leukemia

et al. 2008

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Mutations and chromosomal translocations occur in leukemic cells that result in elevated expression or constitutive activation of various growth factor receptors and downstream kinases. The Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways are often activated by mutations in upstream genes. The Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways are regulated by upstream Ras that is frequently mutated in human cancer. Recently, it has been observed that the FLT-3 and Jak kinases and the phosphatase and tensin homologue deleted on chromosome 10 ( PTEN) phosphatase are also frequently mutated or their expression is altered in certain hematopoietic neoplasms. Many of the events elicited by the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways have direct effects on survival pathways. Aberrant regulation of the survival pathways can contribute to uncontrolled cell growth and lead to leukemia. In this review, we describe the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT signaling cascades and summarize recent data regarding the regulation and mutation status of these pathways and their involvement in leukemia

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Requirement for the PI3K/Akt pathway in MEK1-mediated growth and prevention of apoptosis: identification of an Achilles heel in leukemia

Cited by 58 publications

References 57 publications

Targeting survival cascades induced by activation of Ras/Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways for effective leukemia therapy

Targeting survival cascades induced by activation of Ras/Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways for effective leukemia therapy

Inhibition of phosphatidylinositol 3-kinase dephosphorylates BAD and promotes apoptosis in myeloid leukemias

Contributions of the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to leukemia

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