ライフサイエンスコーパス: A-Raf

1 nduced MEK activation, little is known about A-Raf.

2 nvolvement in the mitochondrial transport of A-RAF.

3 EK-Erk signaling cascade is mediated through A-Raf.

4 n of Raf-1 which in turn is more active than A-Raf.

5 death may occur after an aberrant mitosis by a Raf-1 independent pathway, whereas at higher Taxol con

6 Our results are also consistent with a Raf-1 independent ras activity late in G1, as well as

7 , and conversely a dominant negative Raf and a Raf-1 inhibitor blocked RANTES-induced chemokine trans

8 A Raf-1 mutant with valine substituted for Thr(269) was

9 Interestingly, transient expression of a Raf-1 promoter-reporter construct demonstrates increas

10 Vimentin was not a Raf-1 substrate, but was phosphorylated by Raf-1-assoc

11 sm through which Pak1 signals to BAD through a Raf-1-activated pathway.

12 he intermediate filament protein vimentin as a Raf-1-associated protein.

13 Notably, we show that formation of a Raf-1-Bcl-2 complex coincides with loss of an interact

14 MP mediates the inhibition of MAPK by PKA in a Raf-1-dependent manner.

15 lt of a terminal mitotic arrest occurring by a Raf-1-dependent pathway.

16 by the cytokine, suggesting the presence of a Raf-1-independent, cAMP-insensitive MAPK kinase kinase

17 Here we describe a Raf-1-interacting protein, isolated using a yeast two-

18 ses after Dectin-1 ligation but in part used a Raf-1-mediated pathway to preserve function.

19 RKIP is able to dissociate a Raf-1-MEK complex and behaves as a competitive inhibit

20 operating on transcriptional initiation and a Raf-1-mitogen-activated protein kinase (MAPK) pathway

21 ecipitated Raf-1 to phosphorylate syntide 2, a Raf-1-specific synthetic substrate.

22 , bFGF stimulation promotes the formation of a Raf-1/ASK1 complex at the mitochondria, inhibits ASK1

23 PKD controls interstack Golgi connections in a Raf-1/MEK1-dependent manner, a process required for en

24 Moreover, A-Raf activation, like MEK activation, was blocked by in

25 ent with its previously reported activity as a Raf activator in vitro, PKC alpha functioned similarly

26 stimulated by PC-derived diacylglycerol, as a Raf activator.

27 tment with interferon alfa-2b and sorafenib, a Raf and multiple receptor tyrosine kinase inhibitor, i

28 comprised of three homologous genes, Raf-1, A-Raf and B-Raf [5] which are ubiquitously expressed in

29 Because A-raf and B-raf are expressed similarly in cartilage, we

30 ly, mice with chondrocytes deficient in both A-Raf and B-Raf exhibited normal endochondral bone devel

31 study, the effects of activated Raf (Raf-1, A-Raf and B-Raf) and PI3K/Akt proteins on abrogation of

32 f compensatory increase in the expression of A-Raf and B-Raf.

33 IL-3 activated the alternative Raf isoforms A-Raf and B-Raf.

34 letion by siRNA blocks ERK activity, whereas A-RAF and C-RAF depletion do not affect ERK signalling.

35 Taken together, these results indicate that A-Raf and C-Raf kinases play an important role in regula

36 n partners of two human Raf kinase isoforms, A-Raf and C-Raf, using their N-terminal regulatory domai

37 -kinase inhibitors enhanced CSF-1-stimulated A-Raf and c-Raf-1 activities, and dominant-negative A-Ra

38 ne residues in the protein kinase domains of A-Raf and Raf-1 are important in the regulation of catal

39 erating mice with knockout mutations of both A-raf and raf-1 genes.

40 ve investigated the combined contribution of A-Raf and Raf-1 isotypes to signalling through this path

41 on of K-Ras4a, enhances its interaction with A-Raf, and thus promotes cellular transformation.

42 Ablation of both A-Raf (Araf) and B-Raf (Braf) in chondrocytes does not a

43 er, these results demonstrate that B-Raf and A-Raf are dispensable for endochondral bone development

44 The RAF family members, A-Raf, B-Raf, and C-Raf (or Raf-1), are intermediate mol

45 RAF kinase is a family of isoforms including A-RAF, B-RAF, and C-RAF.

46 h multiple Ras effectors, including c-Raf-1, A-Raf, B-Raf, phosphoinositol-3 kinase delta, RalGDS, an

47 nd c-Raf-1 activities, and dominant-negative A-Raf but not dominant-negative c-Raf-1 reduced CSF-1-pr

48 Myogenic cells cotransduced with RCAS(A)-Raf BXB and RCAS(B)-AFOS remained mononuclear and myo

49 ated protein kinase (ERK) cascade, including A-Raf, c-Raf-1, mitogen-activated protein kinase kinase,

50 c-fos gene was blocked by coexpression with a Raf-C4 catalytic mutant, confirming that HBx induces c

51 Furthermore, we have also identified a Raf-CRD variant that is impaired specifically in its i

52 The A-Raf deficient cells are not disrupted for any of these

53 ssay are both significantly increased in the A-Raf deficient MEFs.

54 c role of A-Raf in this process we generated A-Raf deficient mouse embryonic fibroblasts (MEFs) and e

55 edominantly 129/OLA background, by contrast, A-Raf-deficient animals survived to adulthood, did not d

56 a predominantly C57 Bl/6 genetic background, A-Raf-deficient mice displayed neurological and intestin

57 te Ras activation and Erk phosphorylation in a Raf-dependent but Rac-independent fashion.

58 ent growth-promoting effect on PG cells, and a Raf-dependent step that may involve the transcriptiona

59 effect on RasV12 protection, suggesting that a Raf-dependent, MEK-independent pathway was important f

60 ple downstream signaling pathways, including a Raf-dependent, mitogen-activated or extracellular sign

61 Interestingly, A-Raf does not activate MEK2, although c-Raf can activat

62 However, dominant negative A-Raf effectively blocked MEK activation, suggesting tha

63 signal-regulated kinase (ERK) kinase (MEK), a RAF effector, to induce tumors in vivo in the context

64 ivation, i.e. FD/Delta Raf-1:ER and FD/Delta A-Raf:ER, successfully underwent cell proliferation.

65 act cells via a regulatable upstream kinase, a RAF:estrogen receptor construct, could also inhibit th

66 rs and suggest a model for the regulation of A-raf expression in urogenital tissues.

67 ates ERK cascade signaling by functioning as a Raf family N-Region kinase.

68 dose-dependent reduction (IC50 = 125 nM) in A-Raf gene expression was observed after treatment of ce

69 ss-of-function mutation in the X-chromosomal A-Raf gene, by homologous recombination in embryonic ste

70 To determine whether the human A-raf GREs represent functional motifs, an expression ve

71 Thus, Raf-1 and A-Raf have a combined role in controlling physiological

72 receptors engage and activate both c-Raf and A-Raf in hemopoietic cells.

73 ion, and apoptosis and the potential role of A-RAF in regulating these systems.

74 To investigate the specific role of A-Raf in this process we generated A-Raf deficient mouse

75 n of the Jun NH2-terminal kinases (JNKs) via a Raf-independent pathway, the contribution of JNK activ

76 amic regulation of border cell migration via a Raf-independent pathway.

77 Sorafenib is a RAF inhibitor approved for several cancers, including

78 shc) inhibitor increased ATP content whereas a Raf inhibitor had no effect.

79 To test the hypothesis that sorafenib, a Raf inhibitor used for the treatment of liver and kidn

80 ivation is Ras independent and it signals as a RAF-inhibitor-sensitive monomer.

81 A Raf-inhibitory signal was mapped to a further upstream

82 A-Raf is found to be required for S303 phosphorylation i

83 Our data demonstrated that A-Raf is, indeed, a MEK1 activator and may play a role i

84 in inhibited the EGF-dependent activation of a Raf isoform (B-Raf), lacking an analogous phosphorylat

85 meter: Six mice received 80 mg of sorafenib, a Raf kinase and vascular endothelial growth factor rece

86 s, the suppression of integrin activation is a Raf kinase induced regulatory event that can be mediat

87 ll interfering RNA targeted against B-Raf or a Raf kinase inhibitor (BAY 43-9006) was used to reduce

88 Sorafenib is a Raf kinase inhibitor that could have off-target effect

89 ylation of Ser338 is inhibited by Sorafenib, a Raf kinase inhibitor, but not by the MEK inhibitor U01

90 e inhibitor that was originally developed as a Raf kinase inhibitor.

91 orm of Raf-1, suggesting a critical role for a Raf kinase.

92 tides (ODNs), targeted against rat C-Raf and A-Raf kinases, to reduce gene expression and proliferati

93 INTEGRIN-LINKED KINASE1 (ILK1) that encodes a Raf-like MAP2K kinase with functions insufficiently un

94 ulator constitutive triple response 1 (CTR1, a Raf-like MAPK kinase kinase (MAPKKK)) to activate the

95 opsis has previously been reported to encode a Raf-like mitogen-activated protein kinase kinase (MAPK

96 Arabidopsis AtCTR1 is a Raf-like protein kinase that interacts with ETR1 and E

97 F-1-provoked ERK activation, suggesting that A-Raf mediates a part of the stimulatory signal from Ras

98 Gastrin activated transcription through a Raf-, Mek- and Erk-dependent but Ras-independent pathw

99 s sustained ERK1/2 activation by scaffolding a Raf.MEK.ERK complex associated with the internalized r

100 ppresses the TNF-induced IKK pathway through a Raf/MEK/Erk-independent mechanism.

101 crest development is critically dependent on a RAF/MEK/ERK/serum response factor signaling pathway an

102 ctivity is mediated at least in part through a Raf/ mitogen-activated protein kinase independent path

103 Importantly, this mutant A-Raf molecule is sensitive to inhibition by vemurafenib

104 as found to interact with C-RAF but not with A-RAF N-terminal domain.

105 ved after treatment of cells with the active A-Raf ODN, ISIS 9069, whereas two scrambled controls wer

106 HRP2 levels of >0 U/mL had a RAF of 77% for features of retinopathy combined, with

107 cytes do not have a compensatory increase in A-Raf or B-Raf expression, and thrombopoietin-induced ER

108 only Ras interacted with full-length Raf-1, A-Raf, or B-Raf.

109 vity or Ras-Raf interaction, and that K18 is a Raf physiologic substrate.

110 This implies either that A-Raf plays no role in MEK/ERK activation, that its func

111 ivefold dexamethasone-dependent induction of A-raf promoter activity was observed using constructs co

112 These results demonstrate that the A-raf promoter is regulated in part by members of the gl

113 Interestingly, the human A-raf promoter region contains three potential glucocort

114 DNA sequence analysis of the mouse A-raf promoter region demonstrated that GRE-1 and -2 wer

115 ucocorticoid receptor was cotransfected with A-raf promoter/reporter constructs into HeLa cells.

116 ity in PDAC cells from mice and humans using a Raf pull-down assay.

117 ETR2 acts upstream of CTR1, which codes for a Raf-related protein kinase.

118 We show that Raf-1 and A-Raf require Hsp90 for stability, whereas B-Raf does no

119 interacts with Raf-1 and B-Raf (but not with A-Raf), resulting in the translocation of the Raf protei

120 A-raf shares several functional properties with Raf-1 in

121 In A-Raf the analogous amino acids are also tyrosine wherea

122 A-raf transcripts are predominantly expressed in the mou

123 Although IL-3 did not activate B-Raf, A-Raf was activated by the cytokine.

124 ng Western analysis and immunogold labeling, A-RAF was selectively localized in highly purified rat l

125 forms of the Raf proteins (Raf-1, B-Raf, and A-Raf) were created by ligating NH2-terminal truncated a

126 n proteins, which interact specifically with A-RAF, were identified, and the full-length sequences ar

127 ulted in a rapid and transient activation of A-Raf, which is then capable of phosphorylating and acti