"In a majority of human cancers, the PI3K and AKT pathway is frequently activated by the activating mutations of PI3K p110alpha (PIK3CA) and the loss or inactivating mutation of PTEN, whereas hyper activation of MEK and ERK signaling driven by mutant RAS and BRAF is also a common oncogenic event in a variety of cancers [XREF_BIBR, XREF_BIBR]."
"Papillary and nonpapillary cancers contained similar frequencies of activating RAS mutations (5-10%) [XREF_BIBR], which also function to promote downstream ERK activation."
"The CAM dependent step in the Erk1/2 activation cascade is downstream of Ras activation, because inhibitors of CAM antagonize Erk1/2 activation induced by constitutively activated mutants of Ras and c-Src but not by constitutively activated mutants of Raf and MEK (mitogen and extracellular signal regulated kinase)."
"ERK activation was shown to be dependent on the phosphorylation of the MUC1-CT and could be abolished by a dominant negative Ras mutant or by a MEK inhibitor, thus arguing that the MUC1-CT mediates the Grb2-SOS-Ras-MEK-ERK signaling cascade which leads to cell division."
"MAPK activation induced by the Tpl-2 protein is blocked by dominant negative mutants of Ras and Raf-1, whereas a kinase deficient Tpl-2 mutant down regulates mitogenic signals induced by v-Ha-Ras or v-Raf."
"This contrasts with observations made in the majority of cell models of Ras transformation, in which ectopic expression of mutant Ras causes persistent ERK activation."
"However, none of the TKI resistant cell lines showed mutations of the most affected regions of the genes (amino acids 12, 13 and 60 in K-RAS, amino acids 12, 13, and 61 in N-RAS; data not shown), a finding which was scarcely unexpected because RAS mutations would not only stimulate PI3K, but also ERK1/2 in an imatinib-insensitive manner."
"To validate that ALK and RAS mutations directly activate the RAS and MAPK pathway in neuroblastoma cells, we inducibly expressed an ALK F1174L and an NRAS v61Q mutation in two cell lines that did not harbor RAS MAPK mutations."
"Suppression of Erk activation and in vivo growth in esophageal cancer cells by the dominant negative Ras mutant, N116Y."
"Ras mutations activate the MAPK and PI3K-Akt signaling pathways in thyroid tumorigenesis [XREF_BIBR]."