ライフサイエンスコーパス: GRF1

1 GRF1 can also mediate high frequency stimulation-induced

2 ere examined in transgenic plants carrying a GRF1-GF14 chi promoter-beta-glucuronidase construct.

3 cle was sensitive to the Ras GEFs, Sos1, and GRF1 and to p120 Ras GAP.

4 t functions, WT and various chimeras between GRF1 and GRF2 proteins were tested for their abilities t

5 Oligomers between GRF1 and GRF2 were detected in a rat brain extract, and

6 This led to a significant reduction in both GRF1-dependent ERK phosphorylation and AP1-dependent rep

7 We show that both GRF1 and GRFbeta are expressed selectively in beta cell

8 tional inactivation of oligomer formation by GRF1 is associated with impaired biological and signalin

9 signaling activities, and that in 293T cells GRF1 mediates at least two pathways for Raf activation:

10 lated an Arabidopsis 14-3-3 gene, designated GRF1-GF14 chi (for general regulatory factor1-G-box fact

11 evidence suggesting that the exchange factor GRF1 is upstream of H-Ras activation by alcohol.

12 kb, and the maize general regulatory factor GRF1 gene occupies a domain of 100 kb in length.

13 In search of partner proteins for GRF1, we identified another gene family, GRF-interacting

14 phosphorylation, consistent with a role for GRF1 in calcium-dependent Ras signaling in these cells.

15 ge reaction mechanism by a Ras specific GEF, GRF1.

16 Ras-GRF1 (GRF1) and Ras-GRF2 (GRF2) constitute a family of similar

17 the Ras-specific exchange factors Ras-GRF1 (GRF1) and Ras-GRF2 (GRF2), which are expressed in brain

18 eptors in the CA1 region of the hippocampus, GRF1 promotes LTD, whereas GRF2 promotes theta-burst sti

19 s induction is correlated with a decrease in GRF1, GRF2, and GRF3 transcripts.

20 Introduction of the L263Q mutation in GRF1 led to a protein that was deficient in oligomer for

21 Indeed, GRF1, GRF6, GRF7, GRF12, GRF15, and GRF17 were significa

22 In the absence of free nucleotide, GRF1 could not efficiently stimulate GDP dissociation fr

23 eptides that associate with the DH domain of GRF1.

24 strin homology and/or coiled-coil domains of GRF1 are key to the induction of HFS-LTP by GRF proteins

25 rat brain extract, and forced expression of GRF1 and GRF2 in cultured mammalian cells formed homo- a

26 ated, at least in part, by the expression of GRF1 and possibly other transcription factors of the GRF

27 Finally, the IQ motif of GRF1 determines whether a GRF protein can induce LTD.

28 ein whose N terminus is identical to that of GRF1, a calcium-dependent guanine nucleotide exchange fa

29 smid encoding a dominant negative variant of GRF1 led to 70% reduction in ERK phosphorylation, consis

30 Os-GRF1 (Oryza sativa-GROWTH-REGULATING FACTOR1) was identi

31 Os-GRF1 displays general features of transcription factors,

32 To study its role in plant growth, Os-GRF1 was expressed in Arabidopsis.

33 Our results indicate that Os-GRF1 belongs to a novel class of plant proteins and may

34 Ras-GRF1 (GRF1) and Ras-GRF2 (GRF2) constitute a family of s

35 Ras-GRF1 and Ras-GRF2 constitute a family of calmodulin-regu

36 RAS-GRF1 is a guanine nucleotide exchange factor with the ab

37 Ras-GRF1 plus H-Ras induced a novel, expanded morphology in

38 Ras-GRF1 required coexpression of H-Ras to induce morphologi

39 s-guanine nucleotide-releasing factor 1 (Ras-GRF1) and Ras-GRF2 are highly similar calcium-stimulated

40 s-guanine nucleotide-releasing factor 1 (Ras-GRF1), a neuronal activator of Ras proteins, causes a sp

41 as guanine nucleotide exchange factor 1, Ras-GRF1, by microarray analysis as a c-Jun/AP-1 regulated g

42 of the Ras/ERK pathway partly through a Ras-GRF1 mechanism to modulate the production of MMP-9.

43 CaMKI, the Ca2+-stimulated Ras activator Ras-GRF1 (Ras-guanyl-nucleotide releasing factor), and ERK.

44 showed that beginning at 1 month of age, RAS-GRF1 mediates NMDA-type glutamate receptor (NMDAR)-induc

45 Although both Sos1 and Ras-GRF1 activate the Ras proteins Ha-Ras, N-Ras, and Ki-Ras

46 Tiam1 and Ras-GRF1 are guanine nucleotide exchange factors (GEFs) that

47 These findings imply that Tiam1 and Ras-GRF1 can contribute to Rac signaling specificity by thei

48 ctly represses expression of the Akt and Ras-GRF1 oncogenes.

49 al amino acid exchanges between Sos1 and Ras-GRF1 revealed that the critical amino acids reside withi

50 was significantly inhibited by antisense Ras-GRF1 oligomers.

51 Analysis of chimeras between Ras-GRF1 and Ras-GRF2 demonstrated that a 30-amino acid segm

52 poration of (32)P into Ser(898) of brain Ras-GRF1 following activation of protein kinase A.

53 rdinated activation of H-Ras and Rac1 by Ras-GRF1 may be a significant controller of neuronal cell si

54 onic L-DOPA treatment reveals a complex, Ras-GRF1 and pathway-independent, apparently stochastic invo

55 minate between closely related contexts, RAS-GRF1 begins to contribute to the induction of long term

56 In contrast, Ras-GRF1 mediates signaling from ifenprodil-sensitive (NR2B-

57 ons of the Ras-specific exchange factors Ras-GRF1 (GRF1) and Ras-GRF2 (GRF2), which are expressed in

58 Increases in Ras-GRF1 activity toward Ras that are stimulated by receptor

59 ds (aa) 828-838 in Sos1 and 1057-1067 in Ras-GRF1) of Ras guanine nucleotide exchange factors.

60 Increased Ras-GRF1 expression, in response to inducible c-Jun expressi

61 Full-length Ras-GRF1 that contains an alanine 916 mutation was only part

62 catalytically inactive dominant negative Ras-GRF1, which prevented ERK activation, reduced MMP-9 expr

63 We defined the effects of Ras-GRF1 and truncation mutants that include only one of its

64 es an increase in the phosphorylation of Ras-GRF1 at certain serine residues.

65 espread and selective phosphorylation of Ras-GRF1 at Ser(898).

66 Phosphorylation of Ras-GRF1 at Ser(916) is also required for maximal induction

67 n of the Ras exchange factor activity of Ras-GRF1 by muscarinic receptors.

68 nfirmed the regulated phosphorylation of Ras-GRF1 by Western blotting in both model systems of transf

69 major site of in vivo phosphorylation of Ras-GRF1 in both COS-7 cells and NIH-3T3 fibroblasts.

70 thus could contribute to the function of Ras-GRF1 in neuronal signal transduction pathways that under

71 x, there was striking phosphorylation of Ras-GRF1 in the dendritic tree, supporting a role for Ras ac

72 The activity of Ras-GRF1 is regulated by increases in intracellular calcium

73 ociated with enhanced phosphorylation of Ras-GRF1 on one or more serine residues.

74 A truncation mutant of Ras-GRF1 that included the Rac GEF domains, GRFdeltaC, produ

75 A truncation mutant of Ras-GRF1 that included the Ras GEF domain, GRFdeltaN, plus H

76 Ectopic expression of Ras-GRF1 was accompanied by ERK activation and elevated leve

77 Co-expression of Ras-GRF1 with subtype 1 human muscarinic receptors in COS-7

78 th destabilization and ubiquitylation of Ras-GRF1, a guanine nucleotide exchange factor that activate

79 d not, however, increase the activity of Ras-GRF1, indicating that it is not sufficient for activatio

80 proteins Ha-Ras, N-Ras, and Ki-Ras, only Ras-GRF1 also activates the functionally distinct R-Ras GTPa

81 In addition, Tiam1 or Ras-GRF1 binding to IB2/JIP2 increases the association of th

82 ells potentiates the ability of Tiam1 or Ras-GRF1 to activate the p38 MAP kinase cascade but not the

83 similar functional domain organization, Ras-GRF1 and Ras-GRF2 mediate opposing forms of synaptic pla

84 p140 Ras-GRF1 and p130 Ras-GRF2 constitute a family of calcium/ca

85 exchange factors revealed that both p140 Ras-GRF1 and p130 Ras-GRF2 couple NMDA glutamate receptors (

86 demonstrating an interaction between p75-Ras-GRF1 and Ras.

87 Moreover, p75-Ras-GRF1 could be coprecipitated with a Ras dominant-negativ

88 that c-Jun/AP-1 regulates endogenous p75-Ras-GRF1 expression and that c-Jun/AP-1-regulated anchorage-

89 p75-Ras-GRF1 expression occurred with a concomitant increase in

90 75-kDa c-Jun/AP-1-inducible protein, p75-Ras-GRF1, was detected, and the inhibition of its expression

91 termed 2152) that selectively recognizes Ras-GRF1 when it is phosphorylated at Ser(916/898) confirmed

92 through the calcium/calmodulin regulated Ras-GRF1 and Ras-GRF2 exchange factors, which form AMPA-indu

93 We demonstrate here that Ras-GRF1 is highly expressed in rat brain compared with the

94 The Ras-GRF1 exchange factor has regulated guanine nucleotide ex

95 The Ras-GRF1 exchange factor is strongly implicated in the contr

96 The Ras-GRF1 exchange factor, which is regulated by increases in

97 hat c-Jun/AP-1 can bind and activate the Ras-GRF1 promoter in vivo.

98 ngly, LTP induction by CP-AMPARs through RAS-GRF1 occurs via activation of p38 MAP kinase rather than

99 Here we show that whereas Ras-GRF1 activated both Ha-Ras and R-Ras in cells, Ras-GRF2

100 nduction of NMDAR-dependent LTP, whereas Ras-GRF1 contributes predominantly to the induction of NMDAR

101 eactivity only under conditions in which Ras-GRF1 was phosphorylated at Ser(916/898).

102 ze plants overexpressing miRNA396a-resistant GRF1 support a model proposing that distinct association

103 We conclude that GRF1 and GRF2 can form homo- and hetero-oligomers via th

104 We propose that GRF1 and GIF1 act as transcription activator and coactiv

105 The results suggest that GRF1 plays a role in mediating calcium-dependent signal

106 in Erk activity induced by ionomycin in the GRF1-expressing cells also induced a concomitant increas

107 cus-forming activity on NIH 3T3 cells of the GRF1 DH cluster mutant was reduced, while the L263Q muta

108 -263 to Gln (L263Q) in the N terminus of the GRF1 DH domain abolished the two-hybrid interaction, whi

109 Sequence comparison of the GRF1-GF14 chi genomic clone with other 14-3-3 proteins d

110 ither alone, synergistically potentiated the GRF1-stimulated GDP dissociation from Ras.

111 f ionomycin, 293T cells expressing wild-type GRF1 contained much higher levels of Ras-GTP than contro

112 Compared to wild-type GRF1, the focus-forming activity on NIH 3T3 cells of the

113 t was deficient in oligomer formation, while GRF1 containing the DH cluster mutations formed homo-oli

114 protein was involved in the interaction with GRF1.