ライフサイエンスコーパス: Galphao

1 only serve as GTPase activating proteins for Galphao.

2 (G proteins) and by depletion of Galphaq and Galphao.

3 in vitro translated [35S]methionine-labeled Galphao.

4 lowered expression of G proteins, especially Galphao.

5 a3 and with the active and inactive forms of Galphao.

6 PC-MDCK cells have no detectable Galphao.

7 G proteins Galphai1, Galphai2, Galphai3, or Galphao.

8 apical lateral membrane similar to wild-type Galphao.

9 lphao-MDCK cells consistently coprecipitated Galphao.

10 pathies encodes the major neuronal G protein Galphao.

11 ction is stronger with the GDP-bound form of Galphao.

12 s by activation of the RGS7/RGS11 substrate, Galphao.

13 down of the expression of either Galphat2 or Galphao.

14 een Kir3.2a and RGS4 nor between Kir3.2a and Galphao.

15 uring RGS domain-catalyzed GTP hydrolysis by Galphao.

16 S protein-catalyzed nucleotide hydrolysis by Galphao.

17 S14 exerts GDI activity on Galphai1, but not Galphao.

18 t GRIN1 functions as a downstream target for Galphao.

19 demonstrate GTPase accelerating activity for Galphao.

20 genous Galphai2, Galphao-MDCK cells localize Galphao, (84% similar to Galphai2) in the subapical regi

21 search for novel proteins that interact with Galphao, a mouse brain library was screened using the ye

22 at least one TJ protein, and that activated Galphao accelerates TJ biogenesis without significantly

23 epithelial cells, rat Galphao, Q205Lalphao (Galphao "activated" by point mutation) and plasmid witho

24 Here, we wished to determine whether and how Galphao affects this channel.

25 Pure RGS14 forms a ternary complex with Galphao-AlF4(-) and an AlF4(-)-insensitive mutant (G42R)

26 ecruited to the plasma membrane by activated Galphao-AlF4(-).

27 Expression of Q205L Galphao (Galphao*), an alpha subunit of heterotrimeric guanine nu

28 kinase signaling pathway that is mediated by Galphao and a src-like kinase.

29 Egg laying is inhibited by the G protein Galphao and activated by the G protein Galphaq.

30 partially blocked by antibody to Galphai1 or Galphao and additively blocked by a combination of both

31 A1 receptors differentially use Galphai2 and Galphao and associated downstream effectors.

32 Staining for Galphao and certain other cascade elements decreased onl

33 with Galphai1/Galphaq (but not with Galphas, Galphao and Ga12/13), and that these inactive-state comp

34 units ( approximately 13% FRET), and between Galphao and GABA(B) R1 or R2 subunits ( approximately 10

35 and involvement of Src and Stat3 pathways in Galphao and Galphai mediated transformation of cells.

36 ist-bound state had highest affinity for the Galphao and Galphai2 subtypes (Kd approximately 9 nm and

37 We found that Galphao and Galphaq act directly in the serotonergic HSN

38 by modulating serotonin biosynthesis and (2) Galphao and Galphaq act in the same neurons to have oppo

39 Antiserotonin staining confirmed that Galphao and Galphaq antagonistically affect serotonin le

40 Galphao and Galphaq have opposing effects on many behavi

41 of two pertussis toxin-sensitive G proteins, Galphao and Galphat, for signaling by the Frizzled-2 rec

42 al and biochemical results suggest that both Galphao and Gbetagamma bind TRPM1 channels and cooperate

43 Galphao and Pcp2 binding was confirmed in vitro using gl

44 In addition, when Galphao and Pcp2 were cotransfected into COS cells, Galp

45 We show that WNT signaling through Galphao and PLC-beta results in sustained Ca(2+) release

46 These results indicate that Galphao and Q205Lalphao expressed in MDCK cells are loca

47 is of loss-of-function point mutants of both Galphao and RGS12.

48 epending on the G protein (mild decrease for Galphao and severe for Galphas).

49 e found that RIC-8 stimulates GTP binding by Galphao and that the RGS domain of RGS-7 stimulates GTP

50 t3 can function as a downstream effector for Galphao* and mediate its biological effects.

51 sis, the formation of tight junctions in PC, Galphao, and Q205Lalphao-MDCK cells was followed by meas

52 tissue, we showed that Kir2.4 interacts with Galphao, and this interaction is stronger with the GDP-b

53 Intracellular dialysis of anti-Galphai/Galphao antibodies completely blocked activation of ICat

54 ranes were bound selectively by Galphai1 and Galphao antibodies.

55 In particular, the activation of Galphao appears to be a key factor controlling the Wnt-5

56 competitively inhibited by both Galphai1 and Galphao at nanomolar concentrations when they are bound

57 GRIN1 colocalizes with Galphao at the growth cone of neuronal cells and promote

58 Using a Galphao-betagamma bioluminescence resonance energy trans

59 The Galphao binding region of GRIN1 did not demonstrate GTPa

60 haoQ205L or GRIN1Delta(717-827), which lacks Galphao binding region, promoted microspike formation in

61 S-transferase-fused GRIN1 deletion mutants, Galphao binding regions were localized to amino acid res

62 ls by dark adaptation, phosducin or inactive Galphao (both sequester Gbetagamma) opened the channel w

63 t fraction of inhibition was reduced by anti-Galphao but not by anti-Galphai antibody.

64 plays little GAP activity toward Galphai1 or Galphao, but its activity with Galphaz is competitively

65 ling components included gustducin-alpha and Galphao, but not rod or cone transducin-alpha.

66 34H mutation imparts oncogenic properties to Galphao by accelerating nucleotide exchange and renderin

67 ivation of Go, but rather to the trapping of Galphao by the VCPWE motifs, possibly leading to its dis

68 ng-based studies have shown that Galphai and Galphao can inhibit insulin secretion in pancreatic beta

69 veloped TER significantly faster than PC and Galphao cells in the early phase (0-4 h) (54 +/- 4 versu

70 ith light, a constitutively active mutant of Galphao closed the channel, but wild-type Galphao did no

71 te that the oncogenic R234H mutation renders Galphao constitutively active by accelerating the rate o

72 t carbachol and the heterotrimeric G protein Galphao could activate p38 in 293 cells.

73 D173N) with a counterpart cancer mutation in Galphao (D151N).

74 domain of RGS-7 stimulates GTP hydrolysis by Galphao, demonstrating that Galphao passes through the G

75 pened the channel while the active mutant of Galphao did not.

76 of Galphao closed the channel, but wild-type Galphao did not.

77 t one of the most abundant Galphai proteins, Galphao, did not interact with Eya2.

78 BODIPYFL-GTP bound to Galphao exhibits a 200% increase in fluorescence quantum

79 hao RGSi subunits, there was a small loss of Galphao expression and an accompanying decrease in basal

80 Immunoassays were used to analyze the Galphao expression in mouse pancreatic cells.

81 Furthermore, Galphao* expression increased activity of the tyrosine k

82 ceptors were coupled equally to Galphai2 and Galphao for signaling.

83 To determine whether Pcp2 could modulate Galphao function, kinetic constants kcat and koff of bov

84 S-insensitive (RGSi) mutant Galphao protein, Galphao(G184S) (Galphao RGSi), was evaluated for morphin

85 Galpha subunits Galphas, Galphai2, Galphai3, Galphao, Galpha(q/11), and Galpha13.

86 ability to support pertussis toxin-catalyzed Galphao/Galphai ADP-ribosylation, or its ability to inhi

87 tected for all members of the G(i/o) family (Galphao, Galphai1, Galphai2, Galphai3, Galphaz) as well

88 Expression of Q205L Galphao (Galphao*), an alpha subunit of heterotrimeric g

89 st Galphai but not by those directed against Galphao, Galphaq and Galpha11.

90 ic8A is normally responsible for the Galphai/Galphao, Galphaq, and Galpha12/Galpha13 subfamilies, and

91 The G protein subunits Galphai, Galphao, Galphaq, Galphas, and Gbetagamma all have been

92 ric G protein subfamilies, such as Galphai1, Galphao, Galphas, and Galphaq The FZD4-G protein complex

93 xin and by oligodeoxynucleotide antisense to Galphao, Galphat2, and Gbeta2.

94 Go comprises Galphao , Gbeta3 and a Ggamma.

95 ecifically, the TRPM1 channel and G proteins Galphao, Gbeta5, and RGS11 were progressively lost from

96 ors, including G proteins (Galphas, Galphai, Galphao, Gbetagamma), protein kinases (PKCbetaII, CaMKII

97 ine(243) --> histidine (R243H) in the GNAO1 (Galphao) gene was identified in breast carcinomas and sh

98 To understand the mechanisms of Galphao-GRIN1 pathway, we analyzed functional domains of

99 capacity to stimulate the GTPase activity of Galphao-GTP, demonstrating that RGS14 can functionally e

100 cing the response were coupled to Galphai or Galphao heterotrimeric G proteins.

101 We show that antagonistic Galphao/i and Galphas signaling pathways function in the

102 ce that the D2L dopamine receptor couples to Galphao in neuronal cells, and that this coupling is res

103 f body size, because inactivation of Rdl and Galphao in the motor neurons reduced the larval body siz

104 Conditional deletion of the G protein Galphao in the olfactory system, which leads to impaired

105 l protein-2) was identified as a partner for Galphao in this system.

106 Expression of Galphao* in NIH-3T3 cells activated signal transducer an

107 Galphao inactivation significantly enhances insulin secr

108 s, while after fear conditioning coupling to Galphao increases.

109 ed the binding of RGS7 to the Galpha subunit Galphao, indicating that Gbeta5 is a specific RGS inhibi

110 tivity of the tyrosine kinase c-Src, and the Galphao*-induced activation of Stat3 was blocked by expr

111 ression of dominant negative Stat3 inhibited Galphao*-induced transformation of NIH-3T3 cells and act

112 ma, but not constitutively active Galphai or Galphao, inhibited TRPM3 currents.

113 Galphai1, Galphai3, and Galphao interacted strongly with GAIP, whereas Galphai2

114 energy transfer assays indicated that while Galphao interacts with both the N- and the C- termini of

115 retinal bipolar neurons, two locations where Galphao is also expressed.

116 uggest that the interaction between Pcp2 and Galphao is important to Purkinje cell function.

117 Galphao is not required for endocrine islet cell differe

118 The heterotrimeric G protein Galphao is ubiquitously expressed throughout the central

119 alphai1, Galphai2, and Galphai3) and the two Galphao isoforms (Galphaoa and Galphaob) with potencies

120 ded receptor had highest affinity toward the Galphao (Kd approximately 20 nm) and lowest affinity tow

121 e through glia-specific modulation of moody, galphao, loco, lachesin, or neuroglian-each a well-studi

122 Immunoprecipitates of ZO-1 from Galphao-MDCK cells consistently coprecipitated Galphao.

123 Similar to endogenous Galphai2, Galphao-MDCK cells localize Galphao, (84% similar to Gal

124 In Galphao-MDCK cells, a physical association of Galphao wi

125 rotein-coupled tyrosine kinase pathways, the Galphao-mediated modulation requires neither protein kin

126 Pcp2 stimulates GDP release from Galphao more than 5-fold without affecting kcat.

127 Islet cells differentiate properly in Galphao(-/-) mutant mice.

128 We performed extensive characterization of Galphao mutants, showing abnormal GTP uptake and hydroly

129 Galphao nullizygous beta-cells contain an increased numb

130 +/- 107 versus 437 +/- 37 (PC); 548 +/- 54 (Galphao) Omega.cm2).

131 (117 +/- 10 versus 45 +/- 5 (PC); 66 +/- 7 (Galphao) Omega.m2/h) after Ca2+ switch.

132 h) (54 +/- 4 versus 23 +/- 3 (PC); 12 +/- 1 (Galphao) Omega.m2/h) and late phase (4-h peak) (117 +/-

133 Yet it is unclear whether Galphai and Galphao operate through identical mechanisms and how the

134 ers failed to detect their binding to either Galphao or Galphaq, indicating that the interaction migh

135 contrast, little or no coupling occurred to Galphao or Galphaq.

136 reagents that modify the activity of either Galphao or Gbetagamma and then observing their effects o

137 s of GRIN1 that are involved in binding with Galphao or with its targeting to the plasma membrane.

138 TP hydrolysis by Galphao, demonstrating that Galphao passes through the GTP bound state during its ac

139 t the tyramine receptor SER-2 acts through a Galphao pathway to inhibit neurotransmitter release from

140 pithelium, suggesting that Galphaq, Galphai, Galphao, PLC-like protein, and IP3R may be involved in w

141 Co-expression of constitutively active Galphao prevented the RGS7-RGS7 interaction.

142 t expresses an RGS-insensitive (RGSi) mutant Galphao protein, Galphao(G184S) (Galphao RGSi), was eval

143 sly shown to be directly triggered by active Galphao proteins to promote cellular transformation.

144 ar-naive mice PAR1 couples to Galphaq/11 and Galphao proteins, while after fear conditioning coupling

145 of Galpha subunits in epithelial cells, rat Galphao, Q205Lalphao (Galphao "activated" by point mutat

146 The constitutively active Galphao R243H mutant also enhances Src-STAT3 signaling i

147 ar basis for the oncogenic properties of the Galphao R243H mutant.

148 the enhanced rate of nucleotide exchange in Galphao R243H results from loss of the highly conserved

149 Galphao-R243H binds nucleotides efficiently under steady

150 ading to the loss-of-function in AHO whereas Galphao-R243H has a mild decrease in nucleotide affinity

151 This mutation is structurally analogous to Galphao-R243H, an oncogenic mutant with increased activi

152 We found that, contrary to Galphao-R243H, Galphas-R265H activity is compromised due

153 hat the wild type and the inactive mutant of Galphao reduce the Kir2.4 basal current, whereas the act

154 cence-based assays were used to evaluate how Galphao regulates insulin vesicle docking and secretion

155 Our objective is to examine whether/how Galphao regulates islet development and insulin secretio

156 ortex, and its effects require two redundant Galphao-related G proteins and their nonreceptor activat

157 Infection of NS20Y-D2L cells with HSV-Galphao* rescued both inhibition and sensitization in PT

158 rboxyl-terminal amino acids from Galphai and Galphao, respectively) and that different receptor/G pro

159 Mice expressing Galphao RGSi subunits exhibited a naltrexone-sensitive e

160 spinal cord homogenates from mice expressing Galphao RGSi subunits, there was a small loss of Galphao

161 GSi) mutant Galphao protein, Galphao(G184S) (Galphao RGSi), was evaluated for morphine or methadone a

162 As the strength of Galphao-Ric8B interactions correlates with disease sever

163 ange; however, this mutation does not affect Galphao's ability to become deactivated by GTPase-activa

164 mino acid substitutions spreading across the Galphao sequence.

165 at muscarinic acetylcholine receptor (mAchR)/Galphao signaling produces the sign-inversion required f

166 a targets Kir2.4 to the plasma membrane, and Galphao slows this down by binding Gbetagamma.

167 GABA(B) R1 and R2 receptors, Kir3 channels, Galphao subunits and regulators of G protein signalling

168 ertussis toxin-catalyzed ADP-ribosylation of Galphao subunits, presumably by inhibiting heterotrimer

169 g in neomorphic interactions with pathogenic Galphao through imbalance of the neuronal G protein sign

170 esults suggest that the binding of activated Galphao to GRIN1 induces activation of Cdc42, which lead

171 oteins (Galphai1*, Galphai2*, Galphai3*, and Galphao*) to rescue both responses after PTX treatment.

172 FZD9 forms a precoupled complex with Galphao under basal conditions that dissociates after Wn

173 their interaction with Galphai, Galphat, and Galphao via a G-protein regulatory (GPR) motif that serv

174 Plasma membrane localization of Galphao was decreased for a subset of mutations that lea

175 and Pcp2 were cotransfected into COS cells, Galphao was detected in immunoprecipitates of Pcp2.

176 Galphao was specifically inactivated in pancreatic proge

177 in CHO-hSPR couples to Galphaq, Galphas, and Galphao (), we examined the involvement of various secon

178 etic constants kcat and koff of bovine brain Galphao were determined in the presence and absence of P

179 RGS11 plays a role in the deactivation of Galphao, which precedes activation of the depolarizing c

180 alphao-MDCK cells, a physical association of Galphao with components of the TJ was detectable by immu

181 of Galphai1, Galphai2, and Galphai3, but not Galphao, with Eya2 recruited Eya2 to the plasma membrane