2007
DOI: 10.1016/j.bbamcr.2006.10.001
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Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance

Abstract: Growth factors and mitogens use the Ras/Raf/MEK/ERK signaling cascade to transmit signals from their receptors to regulate gene expression and prevent apoptosis. Some components of these pathways are mutated or aberrantly expressed in human cancer (e.g., Ras, B-Raf). Mutations also occur at genes encoding upstream receptors (e.g., EGFR and Flt-3) and chimeric chromosomal translocations (e.g., BCR-ABL) which transmit their signals through these cascades. Even in the absence of obvious genetic mutations, this pa… Show more

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Cited by 1,936 publications
(1,584 citation statements)
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References 185 publications
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“…This is consistent with data already reporting that P53 expression is decreased in PTENÀ/À cells 30 through the increase of MDM2 activation caused by overexpression of pAKT. In addition to its influence on PI3K activity and consequent inhibition of AKT signaling, P53 could further influence the cell response to P53, PTEN and cetuximab sensitivity S Bouali et al cetuximab through its potential consequence onto PDK1.…”
Section: Discussionsupporting
confidence: 93%
“…This is consistent with data already reporting that P53 expression is decreased in PTENÀ/À cells 30 through the increase of MDM2 activation caused by overexpression of pAKT. In addition to its influence on PI3K activity and consequent inhibition of AKT signaling, P53 could further influence the cell response to P53, PTEN and cetuximab sensitivity S Bouali et al cetuximab through its potential consequence onto PDK1.…”
Section: Discussionsupporting
confidence: 93%
“…This ineffectiveness was probably due to Akt/Erk phosphorylation and activation during treatment as their level increased upon treatment. Similar indicators of resistance mechanisms have been observed both in cell lines and in biopsies from cancer patients treated with inhibitors of relevant pathways [80, 81]. …”
Section: Potential Targetable Pathwayssupporting
confidence: 65%
“…These observations suggest the involvement of ERK1 in giardial mSREBP phosphorylation. Considering MAPK activation by the dual specificity MAPK kinases 1 and 2 (MAPKKs = MEK1/2; McCubrey et al, 2007), there is one giardial homolog of MEK1 (STE20 type) in the GiardiaDB (orf 22165) ( Table I). The sequences of human (393 aa long) and giardial (357 aalong) MEK1s show at most 39 % identity and 56 % homology (e.v.…”
Section: Cell Signaling In Giardial Encystation: Experimental and Biomentioning
confidence: 99%
“…human v-Raf-1, 648 aa-long) is atypical or truncated since the putative giardial homolog is shorter than the Raf-related G. gallus sequence displaying this domain (606 vs 1346 aa, respectively). In addition Raf-related sequences, including giardial Raf1-like, lack a Ras-binding domain (RBD) that allows Ras-mediated Raf translocation to cell membrane (McCubrey et al, 2007). To date one putative RBD has been described in the phosphatidylinositol-3-kinase-1 (PI3K1) sequence of this protist (Cox et al, 2006) and a Ras-like GTPase sequence was reported in the annotated GiardiaDB (orf 9718) suggesting that Ras-like is preferentially involved in the partially characterized PI3K signaling pathway of G. duodenalis (Cox et al, 2006;Morrison et al, 2002).…”
Section: Cell Signaling In Giardial Encystation: Experimental and Biomentioning
confidence: 99%
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