IndraLab

Statements


1 16 6 | 2 25 42

reach
"An alternative possibility is that adhesion dependent PAK1 activation and subsequent phosphorylation of MEK1 on S298 is sufficient to stimulate MEK1 phosphorylation and activation by low levels of c-Raf activity merely by enhancing the interaction between c-Raf and MEK1."

sparser
"Overexpression of activated forms of c-Raf and MEK1 (a component of the mitogen-activated protein kinase pathway, MAPK) led to cell dissociation, as inferred by the loss of desmosomes from the cell periphery."

reach
"Moreover, cisplatin dissociates cRaf from MEK1 in a dose dependent manner in vitro using purified MEK1 and cRaf complex isolated from KB-3-1 cells by MEK1 immunoprecipitation, suggesting that cisplati[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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sparser
"We propose that direct interaction of C-Raf and MEK-1 contributes to C-Raf activation by inducing C-Raf hyper-phosphorylation, either by conferring a conformation that is more susceptible to phosphorylation or by stabilizing the phosphorylated form of C-Raf."

sparser
"NEK10 forms a complex with RAF1 and MEK1 and acts as a positive regulator of ERK1/2 (Extracellular signal-regulated protein kinases 1 and 2) after UV irradiation [ xref ]."

reach
"We propose that direct interaction of C-Raf and MEK-1 contributes to C-Raf activation by inducing C-Raf hyper-phosphorylation, either by conferring a conformation that is more susceptible to phosphorylation or by stabilizing the phosphorylated form of C-Raf."

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sparser
"Its expression in tumor cells is further enhanced upon tumor necrosis factor (TNF) alpha treatment, whereas hPEBP4 normally co-localizes with lysosomes, TNFalpha stimulation triggers its transfer to the cell membrane, where it binds to Raf-1 and MEK1."

reach
"Thus, in this oligodendrocyte enriched glial cell population, Raf-1 can bind to MEK1 in the absence of B-Raf but can not take its place as a MEK kinase or stimulate MEK 's association with KSR, which ultimately results in impaired ERK phosphorylation (XREF_FIG)."

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sparser
"Delphinidin directly binds with Raf1 or MEK1 noncompetitively with ATP."

sparser
"We also show that the integrity of the Raf ATP-binding site is necessary for the interaction between Raf-1 and MEK1."

sparser
"Transfection of the dominant-active form of Raf-1 (Ad-daRaf-1) or MEK1 (Ad-daMEK1) inhibited 1,25(OH)(2)D3-dependent cystatin A promoter activity and its expression."

reach
"82 In this orthotopic model, the enhanced recruitment of C-Raf and B-Raf to MEK1 was observed."

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reach
"This could be because the interaction between CRAF and MEK1 is different than that between BRAF and MEK1 or because DoMY-Seq failed to capture that second binding motif."

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sparser
"These results indicated that delphinidin interacts with Raf1 or MEK1, and results in downregulation of their respective kinase activities."

sparser
"Disruption of the interaction between Raf-1 and MEK1, leads to an inhibition of MEK phosphorylation and activation by Raf-1."

sparser
"Phosphorylation of MEK1 on serine 298 does not appear to regulate the interaction between Raf-1 and MEK1, but rather the ability of Raf-1 to phosphorylate MEK1 with which it is complexed in vivo."

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sparser
"In addition, though MEK-1 was able to induce C-Raf phosphorylation at the S338 site, which was shown to play a role in C-Raf activation by certain growth factors [ xref ], MEK-1 was able to bind and activate the S338/339A C-Raf mutant, suggesting that the MEK-1-induced C-Raf activation does not require phosphorylation at these sites ( xref , lanes 4, 5, left panel and lanes 6–9, right panel)."

sparser
"This result indicates that MEK-1 binding to C-Raf is required for the enhanced C-Raf phosphorylation, suggesting that MEK-1 may confer a C-Raf conformation that is more accessible to phosphorylation or is protected from dephosphorylation."

reach
"We also found ex vivo binding between delphinidin and Raf1 or MEK1 in JB6 P+ cell lysates (XREF_FIG)."

sparser
"We optimized DoMY-Seq by taking advantage of the well-described and high-affinity interaction between KRAS and CRAF, and we provide high resolution domain mapping on this and other protein interacting pairs, including CRAF-MEK1, RIT1-RGL3, and p53-MDM2."

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sparser
"Pull-down and competition assays revealed that delphinidin binds with Raf1 or MEK1 noncompetitively with ATP."

sparser
"Several molecular mechanism underlying this modulation have been proposed including enhanced interaction between MEK1 and Raf-1 [36] , priming of MEK1 for its activation by Raf-1 [37] , promotion of[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Furthermore, additional studies suggest that EGCG can also decrease the phosphorylated forms of ERK and mitogen activated protein (MEK1) through its oxidative stress inhibition of the association between Raf-1 and MEK1 and ERK kinase1, leading to suppression of proliferation of the HT29 human colon cancer cell line XREF_BIBR."

sparser
"In agreement with this, SPR using purified proteins showed that cisplatin binding to MEK1 weakens the interaction of MEK1 with cRaf, but not MAST1 ( xref )."

sparser
"In the course of studying C-Raf-MEK-1 interactions, we noticed that coexpression of C-Raf with MEK-1 results in a significant mobility shift in C-Raf, suggesting that MEK-1 could induce increased C-Raf phosphorylation [ xref ]."

sparser
"Conversely, NFAT activity was stimulated by expression of constitutively active forms of c-Raf or MEK1."

sparser
"Since the dissociation of cRaf from MEK1 induces MAST1 to reactivate the MAPK pathway, any cellular events that affect cRaf-MEK1 binding may activate MAST1-dependent MEK1 activation."

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reach
"Consistently we found that, although MAST1 is present in the cRaf and MEK1 complex, cancer cells depend on cRaf dependent MEK1 activation to promote proliferation and tumor growth."

sparser
"DUSP2 rs1724120 [hazard rate ratio (HRR) = 0.72, 95%CI = 0.54, 0.96; AA versus GG/GA), MAP3K10 rs112956 (HRR = 1.40, 95% CI = 1.10, 1.76; CT/TT versus CC) and MAP3K11 (HRR = 1.76, 95% CI 1.18, 2.62 TT versus GG/GT) influenced survival after diagnosis with colon cancer; MAP2K1 rs8039880 (HRR = 2.53, 95% CI 1.34, 4.79 GG versus AG/GG) and Raf1 rs11923427 (HRR = 0.59 95% CI = 0.40, 0.86; AA versus TT/TA) were associated with rectal cancer survival."

reach
"It has been shown that Raf-1 and B-Raf interact with both MEK1 and MEK2."

reach
"Specifically, activated Pak1 can phosphorylate Mek1 at Ser298 to enhance the stable association between Raf-1 and Mek1 22, and Pak1 can also phosphorylate Ser338 in the Raf-1 catalytic domain to enhance Raf-1 kinase activity 25."

sparser
"Pull-down assays revealed that RWE or quercetin (but not resveratrol) bound with either MEK1 or Raf1."

reach
"Phosphorylation of 338SSYY341 regulates specific interaction between Raf-1 and MEK1."

reach
"Moreover, the C142A MEK1 neither separated cRaf from MEK1 and cRaf complex nor attenuated MEK activity in cells in response to cisplatin, suggesting that cisplatin binds MEK1 and directly promotes the[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"Summary: Raf-1 is a MAP kinase kinase kinase (MAP3K) which functions downstream of the Ras family of membrane associated GTPases to which it binds directly. Once activated Raf-1 can phosphorylate to activate the dual specificity protein kinases MEK1 and MEK2 which in turn phosphorylate to activate the serine/threonine specific protein kinases ERK1 and ERK2. Activated ERKs are pleiotropic effectors of cell physiology and play an important role in the control of gene expression involved in the cell division cycle, apoptosis, cell differentiation and cell migration."

reach
"PAK1 phosphorylates MEK1 on Ser298, a site important for binding of Raf-1 to MEK1 in vivo."

sparser
"Of relevance to such possibilities are earlier studies that have shown that Raf1 forms a signaling complex with MEK1, but not MEK2 ( xref ), and that MEK and ERK form a complex together with a scaffold protein that apparently has a preference for MEK1 ( xref ; xref )."

reach
"Activated Pak phosphorylates Mek1 at Ser298, one of two sites in the catalytic domain thought to be important for stable association between Raf1 and Mek1 7,44,45."

reach
"Phosphorylation of MEK1 on serine 298 does not appear to regulate the interaction between Raf-1 and MEK1, but rather the ability of Raf-1 to phosphorylate MEK1 with which it is complexed in vivo."

sparser
"The NEK10 protein acts as a positive regulator of ERK1/2 (Extracellular signal-regulated protein kinases 1 and 2), after UV irradiation and forms a complex with RAF1 and MEK1."

reach
"The specific structure of cisplatin may disrupt the MEK1 and cRaf complex, resulting in MAST1 as the sole kinase remaining in the complex."

reach
"We also show that the integrity of the Raf ATP binding site is necessary for the interaction between Raf-1 and MEK1."

sparser
"The MAPK pathway is activated in differentiating muscle cells and expression of constitutively active form of MEK1 or Raf1 enhances the transcriptional activity of MyoD ."

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sparser
"Here we have defined the regions of JSAP1 responsible for the interactions with MEK1 and Raf-1."

sparser
"In H- ras transformed mouse epidermal cells, EGCG directly causes a decrease in the activation of ERK and MEK1, a decrease in the association of Raf-1 with MEK1, and the inhibition of the AP-1 activity [ xref ]."

sparser
"In this study overexpression of activated forms of c-Raf and MEK1 led to cell dissociation through the loss of desmosomes from the cell periphery."

reach
"Disruption of the interaction between Raf-1 and MEK1, leads to an inhibition of MEK phosphorylation and activation by Raf-1."

reach
"Moreover, the overexpression of MEK1 (3A) failed to block endogenous MEK1 activation, although MEK1 (3A) formed complexes with both c-Raf and B-Raf as well as p42 and p44 MAPK."

sparser
"RAF1 interaction regulates free β-catenin, but we have also shown that MST2 and LATS1 regulate the RAF1-MEK1 interaction and signalling in a RASSF1A dependent manner [ xref , xref ]."

sparser
"An alternative possibility is that adhesion-dependent PAK1 activation and subsequent phosphorylation of MEK1 on S298 is sufficient to stimulate MEK1 phosphorylation and activation by low levels of c-Raf activity merely by enhancing the interaction between c-Raf and MEK1."

sparser
"Because delphinidin can inhibit Raf1 or MEK1 activity, we determined whether delphinidin directly interacts with Raf1 or MEK1."

reach
"This result indicates that MEK-1 binding to C-Raf is required for the enhanced C-Raf phosphorylation, suggesting that MEK-1 may confer a C-Raf conformation that is more accessible to phosphorylation or is protected from dephosphorylation."

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sparser
"Two lines of evidence suggest that the MAPK cascade induces the activity of MyoD: 1) the expression of constitutively activated forms of MEK1 or Raf1 enhanced the transcriptional activity of MyoD in 10T1/2 fibroblasts; and 2) the addition of PD098059 to fibroblast cells expressing a conditional MyoD-estrogen fusion protein significantly inhibited the expression of MyoD-responsive genes."

trips
"PAK1 phosphorylates MEK1 on Ser298, a site important for binding of Raf-1 to MEK1 in vivo."

sparser
"We optimized DoMY-Seq by taking advantage of the well-described and high-affinity interaction between KRAS and CRAF, and we provide high-resolution domain mapping on this and other protein-interacting pairs, including CRAF-MEK1, RIT1-RGL3, and p53-MDM2."

reach
"Several molecular mechanism underlying this modulation have been proposed including enhanced interaction between MEK1 and Raf-1 [36], priming of MEK1 for its activation by Raf-1 [37], promotion of a m[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"We note that NIMA gene-family Neks have been previously implicated in the regulation of various aspects of the cell cycle and that Nek-10 is physically associated with Raf-1 and MEK1, formation of the three-protein complex being necessary for Nek-10-mediated MEK1 autoactivation [ xref , xref ]."

reach
"Active PAK1 (structurally very similar to PAK2) also phosphorylates MEK1, a mammalian MAP2K, at Ser298, which is important for the stable binding of MEK1 and Raf-1 19."

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sparser
"An isoform of MEK1 was found associated with the complex when Raf-1 is overexpressed [154], and the association of MEK1 with Raf-1 in a complex is dependent on the ac- tivity of p21ras."

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sparser
"Active PAK1 (structurally very similar to PAK2) also phosphorylates MEK1, a mammalian MAP2K, at Ser298, which is important for the stable binding of MEK1 and Raf-1 19 [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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sparser
"Delphinidin binds with Raf1 and MEK1 and strongly inhibits their kinase activity."

sparser
"Also, in vitro and ex vivo pull-down assays revealed that delphinidin directly bound Raf1 and MEK1 noncompetitively with ATP, which might account for reduced kinase activities of Raf1 and MEK1."

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reach
"We previously demonstrated that cisplatin also binds to MEK1 at C142 that mediates disruption of the MEK1-cRaf complex allowing MAST1 to serve as a substitute for cRaf in MAPK signaling ."

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sparser
"PAK1 phosphorylates MEK1 on Ser298, a site important for binding of Raf-1 to MEK1 in vivo."

sparser
"This could be because the interaction between CRAF and MEK1 is different than that between BRAF and MEK1 or because DoMY-Seq failed to capture that second binding motif."

sparser
"This sequence in MEK1 contains phosphorylation sites not present in MEK2 and has been shown to be necessary for MEK1 to interact with C-Raf and for MEK1 activation in cells."

sparser
"The overexpression of the activated forms of c-Raf and MEK1 leads to cell dissociation."

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trips
"Through interaction with Raf-1, RKTG changes the localization of Raf-1 from cytoplasm to the Golgi apparatus, blocks EGF-stimulated Raf-1 membrane translocation, and reduces the interaction of Raf-1 with Ras and MEK1."

reach
"Using an in vitro system, enhanced recruitment of B-Raf and c-Raf to MEK1 occurred only when both MAT2B and GIT1 were present."

sparser
"This phosphorylation, which occurs in a proline-rich insert in the catalytic domain, has no effect on MEK activity but rather influences the interaction of MEK1 with Raf-1."

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