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Mutated RAS activates ERK. 52 / 52
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"Oncogenic RAS mutations and the BRAF V599E mutation induce constitutive ERK activity when cDNAs encoding the mutant versions are expressed in tissue culture cells."
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"XREF_BIBR RAS mutations hyperactivate PAK1 and initiate PAK1 and ERK or PAK1 and PI3K cascades."
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"Ras mutation results in constitutive activation of Erk1/2 and PI3K and Akt pathways leading to increased cell proliferation and decreased apoptosis in pancreatic cancer cells."
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"Whereas a RAS mutation in other carcinomas might activate both ERK and PI3K signaling, we propose that prostate tumors have an alternative way to activate these pathways : PTEN deletion (PI3K and AKT activation) coupled with oncogenic ETS-overexpression (activation of RAS and ERK target genes)."
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"It has been shown that the oncogenic Ras mutant, RasV12, activates ERK1/2 strongly, and that the constitutively active MEK5 mutant, MEK5D, selectively activates ERK5 XREF_BIBR, XREF_BIBR."
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"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]."
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"RAS mutations constitutively activate MAPK/ERK pathway, as shown in Figure 1C.Interestingly, some studies have also reported somatic oncogenic mutations in normal endometrium and breast cells of healthy women [7, 8]."
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"Mutant RAS activated ERK at comparable or lower levels in sorted GMPs than in CMPs or HSC/MPPs transduced with SA + R and expressing similar levels of all transgenes (Extended Data Fig. 6a,b)."
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"Thus, it is assumed that the mutation of Ras finally cause the constitutive activation of the ERK signal transduction pathway."
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"ERK MAPK activation induced by the Tpl2 protein is blocked by dominant negative mutants of Ras and Raf-1, and a kinase deficient Tpl2 mutant downregulates mitogenic signals induced by v-Ha-Ras or v-Ra[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"These results support a scenario whereby mutant RAS leads to comparable ERK signalling activation in GMPs as in more primitive HSPCs, but with different transcriptional output, upregulating a distinct set of genes that are primed at the chromatin level in the GMP state."
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"Cotransfection of RasN17, a dominant negative Ras mutant, prevented DA induced activation of both ERK and JNK."
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"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)."
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"The RAS mutations resulted in persistent activation of MAPK and ERK in these cells despite FLT3 inhibition."
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"13,20–23 Perhaps ERKs are activated by over-expression of EGF and ras mutation resulting in the accumulation of protein."
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"The dysregulation of these pathways is very common in many cancer types : Receptor Tyrosine Kinases (RTKs) amplification and mutations, PIK3CA or Ras mutations, and loss-of-function mutations in negative regulators such as PTEN, collaborate to constitutively activate either PI3K and Akt or Ras and ERK signaling coupled to mTOR signaling."
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"Nevertheless, a dominant negative mutant of Ras, Ras DN, completely blocked the stochastic ERK activity pulses."
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"In addition, a lack of sensitivity to MEK inhibition is consistent with the observation that mutant Ras often does not drive aberrant activation of ERK in cancer cells XREF_BIBR."
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"We show that ERK activation caused by oncogenic mutants of RAS, RAF, and MEK inhibits RAR signaling in breast cancer cells."
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"WNT signalling is known to play a crucial role in thyroid carcinogenesis, and several mechanisms of its deregulation have been described, including inhibition of the β-catenin degradation complex via its phosphorylation by RET/PTC, inhibition of E-cadherin expression through the MAPK/ERK pathway activated by BRAF mutations, and activation of both canonical and non-canonical Wnt pathways by RAS mutations ."
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"Dominant negative mutants of Ras (but not Rac or Cdc42) specifically inhibited ERK activation by v-Fps and Myr-Fes, demonstrating that ERK activation occurs exclusively downstream of Ras."
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"ERK on the other hand is activated mainly by the mutant RAS, while inhibited by another feedback mechanism through CRAF."
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"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."
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"Perhaps not surprisingly then, the earlier assumptions that pharmacologic inhibition of ERK activation at the level of either Raf or MEK would be equivalent, and would be effective to block ERK activation driven by mutant Ras, have proven incorrect."
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"Given that a variety of tumors activate the MAPK/ERK pathway either by Ras mutation, PTEN loss or EGFR mutation a recent report showed that activation of this pathway resulted in increased migration o[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"That more robust ERK activation is deleterious to cancer development is also supported by the nonoverlapping occurrence of RAS mutations with mutations in BRAF, NF1, or EGFR (cBioPortal)."
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"SDF-1-induced activation of small GTPases Ras, Rap1, and Rac was also enhanced by CrkL overexpression, while a dominant negative mutant of Ras or Rac significantly inhibited Erk activation as well as [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In agreement with our previous work ( Paquin et al., 2005; Bartkowska et al., 2007 ), more than 80% of the cells that expressed EGFP also expressed H-Ras, indicating the reliability of the cotransfect[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"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."
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"These results reinforce the notion that an activating Ras mutation, as present in PANC-1 cells, is not sufficient to constitutively activate the ERK pathway."
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"Ectopic expression of the constitutively active mutant Ras form N-RasD12 in autoreactive cells raises active Erk, halts receptor editing via PI3 kinase, and promotes differentiation via Erk, breaking central tolerance."
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"Papillary and nonpapillary cancers contained similar frequencies of activating RAS mutations (5-10%) [XREF_BIBR], which also function to promote downstream ERK activation."
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"Nevertheless, a dominant negative mutant of Ras suppressed the ERK activity pulses, strongly suggesting that the noise is evoked at the level of Raf binding to Ras."
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"RAS mutants only moderately elevate ERK activity, and only without stimulation."
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"MRAS targets SHOC2-PP1 to dephosphorylate the S259 site of RAF proteins when bound to other molecules of RAS (or RRAS members) and plays a critical contribution to ERK activation by RTKs and mutant RA[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"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."
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"These results suggest that the wild-type p53 has a weak effect on RAS expression and that the RAS mutants V12, S35 and E38 activate the ERK cascade and weaken p53 activity to promote proliferation and apoptosis resistance, while C40 activates the AKT cascade and has little effect on p53 expression and thus inhibits anti-apoptotic processes and proliferation."
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"In fact, 85-90% of papillary carcinomas possess RET, NTRK1, BRAF or RAS mutations that induce MEK and ERK signaling."
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"Most oncogenic activities that lead to constitutive activation of ERK1/2 signalling occur upstream of ERK1/2 activation, including overexpression of receptor tyrosine kinases such as epidermal growth factor receptor (EGFR), activating mutations in receptor tyrosine kinases, sustained autocrine or paracrine production of activating ligands, as well as Ras mutations and B-Raf mutations, resulting in enhanced or constitutive downstream activation of the Raf-MEK-ERK pathway."
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"In a simple linear view of RAS‐to‐ERK transduction, the mutant RAS GTPase activities being 50‐ to 800‐fold lower than wild type would be expected to produce correspondingly large changes in both pre‐stimulus and stimulated ERK activity."
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"Oncogenic RAS mutations, which activate both the RAF-MAPK/ERK (mitogen-activated protein kinase) and phosphoinositide 3-kinase (PI3K)-AKT signalling pathways, are among the most prevalent genetic changes found in human cancers, occurring in approximately 20% of human tumors [13,14]."
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"Conversely, dominant negative mutant of Ras inhibited the protective effects of ERK."
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"First, our systematic dataset reconciles previously conflicting observations of ERK activity driven by RAS mutations."
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"The abilities of dominant negative mutants of Ras and Rac to inhibit SDF-1-induced Erk activation also agreed with their inhibitory effects on chemotaxis ( Figs."
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"Ras mutations are common oncogenic alterations in many cancers and ultimately activate ERK1/2 pathway [ 20 , 21 , 24–27 ]."
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"Specifically, the dual-specificity phosphatase DUSP6/MKP3, which acts as a negative feedback regulator of ERK activity, requires continuous production in an eIF4F-dependent manner to limit excessive ERK signaling driven by oncogenic RAF/RAS mutations."
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"Similarly, M-Ras, with its ability to activate both the MAPK and PI3K pathways, is an excellent candidate gene to be found mutated in human cancer.In cell lines derived from a wide variety of tumor ty[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Given that PI3K/RAS mutations activate MEK/ERK signaling, we investigated MEK/ERK‐transcriptional output and negative feedback regulators."
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"Suppression of Erk activation and in vivo growth in esophageal cancer cells by the dominant negative Ras mutant, N116Y."
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"Furthermore, PLX4032 may enhance the growth of tumors in which the ERK pathway is activated by RAS mutation or upstream receptor kinases."
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"When mutant RAS isoforms were compared with wild-type RAS within an isogenic ‘RAS-less' background, the major change in ERK dynamics driven by RAS mutants was a higher baseline activity that reduced the amplitude of ERK activity upon growth factor stimulation (Figure 3B) [110]."
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"Co-expression of wild-type Aurora-A and mutant Ras enhances the signaling of the MEK and ERK, AKT and RalA activity."
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