ライフサイエンスコーパス: GPIb-IX

1 GPIb-IX activates not only the transfected alpha(IIb)bet

2 GPIb-IX-induced ERK2 phosphorylation is inhibited by PKG

3 GPIb-IX-V is a catch bond for it becomes more stable as

4 n and because no dissociation of the ABP-280/GPIb-IX complexes is detected after thrombin activation.

5 ological role of GPIbbeta phosphorylation, a GPIb-IX mutant replacing Ser(166) of GPIbbeta with alani

6 nphosphorylated identical peptide, abolished GPIb-IX binding to 14-3-3zeta.

7 so showed reduced actin polymerization after GPIb-IX-mediated platelet aggregation, actin polymerizat

8 r botrocetin)-induced vWF binding and allows GPIb-IX-expressing cells to adhere to immobilized vWF un

9 coexpressing integrin alpha(IIb)beta(3) and GPIb-IX adhere and spread on vWF, which is inhibited by

10 rmed for platelet GPla (integrin alpha2) and GPIb-IX-V, but there is support for the 807 T/C polymorp

11 cluding P-selectin, activated GPIIb,IIIa and GPIb-IX), whole-blood platelet aggregation, platelet cou

12 esting that the membrane skeleton-associated GPIb-IX is in a state that prevents access to the A1 dom

13 ires a minimum of two steps, one associating GPIb-IX to the activated cytoskeleton and the second req

14 In this study, the interaction between GPIb-IX and recombinant 14-3-3zeta is reconstituted.

15 than promoted activation of alphaIIbbeta3 by GPIb-IX-V and blocked aggregate formation on collagen at

16 thways in the activation of alphaIIbbeta3 by GPIb-IX-V.

17 rotein Ib-IX-V complex (GPIb-IX), but not by GPIb-IX-independent platelet agonists.

18 atelets show an enhanced reaction to certain GPIb-IX-independent agonists.

19 telet von Willebrand factor receptor complex GPIb-IX-V).

20 d the von Willebrand factor receptor complex GPIb-IX-V, which are essential for thrombus growth and s

21 receptor, the glycoprotein Ib-IX-V complex (GPIb-IX), but not by GPIb-IX-independent platelet agonis

22 The platelet glycoprotein Ib-IX-V complex (GPIb-IX-IV) is the receptor for VWF and is responsible f

23 Akt1 and Akt2 play important roles in early GPIb-IX signaling independent of Syk, adenosine diphosph

24 Cells expressing GPIb-IX adhere to vWF in the presence of botrocetin but

25 ts of Chinese hamster ovary cells expressing GPIb-IX complexes containing wild-type or mutant GPIbalp

26 ld type 14-3-3zeta has a higher affinity for GPIb-IX complex than recombinant GPIbalpha cytoplasmic d

27 dimerization and decreases its affinity for GPIb-IX.

28 therefore necessary, but not sufficient for GPIb-IX centralization.

29 omain before the dissociation of VWF-A1 from GPIb-IX.

30 nst cell-specific glycoproteins (GPIIb-IIIa, GPIb-IX and others) accelerate platelet destruction.

31 /y) platelets exhibited a marked decrease in GPIb-IX-V function and agonist-mediated integrin alphaII

32 me, a bleeding disorder caused by defects in GPIb-IX-V.

33 tification of the mechanosensitive domain in GPIb-IX has significant implications for the pathogenesi

34 unfolding of the mechanosensitive domain in GPIb-IX, which may possibly contribute to platelet mecha

35 mutant complexes confirmed its existence in GPIb-IX and enabled localization of this quasi-stable me

36 s, 14-3-3 binding to GPIb-IX is important in GPIb-IX signaling.

37 model, and show that 14-3-3 is important in GPIb-IX signaling.

38 rotein kinase (MAPK) pathway is important in GPIb-IX-dependent activation of platelet integrin alpha(

39 indicate that Lyn is critically important in GPIb-IX-mediated activation of the cGMP pathway.

40 sphoinositol 3-kinase (PI3K) is important in GPIb-IX-mediated signaling.

41 The defect of LIMK1(-/-) platelets in GPIb-IX-mediated platelet activation is attributed to a

42 vitro leads to the concomitant reduction in GPIb-IX complex expression due to ER-associated degradat

43 n outside-in signaling distinct from that in GPIb-IX-mediated inside-out signaling.

44 These results indicate that thrombin-induced GPIb-IX centralization requires a minimum of two steps,

45 (SFKs) play an important role in VWF-induced GPIb-IX signaling.

46 ermeant calcium chelator Quin-2 AM inhibited GPIb-IX centralization by 70%, but did not prevent its a

47 e 14-3-3-binding site in GPIbalpha inhibited GPIb-IX-mediated fibrinogen binding to alpha(IIb)beta(3)

48 Anti-pS609 inhibited GPIb-IX binding to the intracellular signaling molecule,

49 n to the activated cytoskeleton and inhibits GPIb-IX centralization by 50%, without affecting actin a

50 or vWF interaction with different integrins, GPIb-IX-mediated activation of alpha(IIb)beta(3) require

51 to the platelet membrane glycoprotein Ib-IX (GPIb-IX) results in platelet activation.

52 s receptor, the platelet glycoprotein Ib-IX (GPIb-IX), and p38 inhibitors diminish platelet aggregati

53 Willebrand factor (vWF), glycoprotein Ib-IX (GPIb-IX), mediates initial platelet adhesion and activat

54 d factor (vWF) receptor, glycoprotein Ib-IX (GPIb-IX), mediates platelet adhesion and induces signali

55 o its platelet receptor, glycoprotein Ib-IX (GPIb-IX), via the protein kinase G (PKG) signaling pathw

56 hear sensing and provide a mechanism linking GPIb-IX to platelet clearance.

57 Thus, Akt1 and Akt2 mediate GPIb-IX signaling via the cGMP-dependent signaling pathw

58 plays a novel role in selectively mediating GPIb-IX-dependent TXA2 synthesis and thrombosis and repr

59 The cytoskeletal association of GPIb-IX involves ABP-280, as it correlates with the inco

60 fecting actin assembly or the association of GPIb-IX to the cytoskeleton.

61 ledge, mechanism in which the catch bonds of GPIb-IX-V/VWF can be supported by internal forces produc

62 Because the centralization of GPIb-IX is inhibited by cytochalasin, it is believed to

63 Dephosphorylation of GPIb-IX with potato acid phosphatase inhibited anti-pS60

64 ent with romiplostim decreased expression of GPIb-IX-V complex and GPVI, but not of GPIIbIIIa, and bl

65 mbrane skeleton-associated and free forms of GPIb-IX.

66 e, activation of the VWF binding function of GPIb-IX induced by GPIbbeta dephosphorylation is diminis

67 We show here that the receptor function of GPIb-IX is regulated intracellularly via its link to the

68 sm that controls the VWF binding function of GPIb-IX, and also suggest a new type of antiplatelet age

69 However, the incorporation of GPIb-IX into the cytoskeleton is complete within 1 minut

70 trate that signals induced by interaction of GPIb-IX with von Willebrand factor lead to alpha(IIb)bet

71 have further characterized the mechanism of GPIb-IX centralization in platelets in suspension.

72 The movement of GPIb-IX to the cytoskeleton of activated platelets is th

73 ype and filamin binding-deficient mutants of GPIb-IX is comparable, suggesting that the membrane skel

74 sensitive domain in the GPIbalpha subunit of GPIb-IX was identified.

75 pulling of the A1 domain of VWF (VWF-A1) on GPIb-IX captured by its cytoplasmic domain induced unfol

76 P elevation, and their inhibitory effects on GPIb-IX-dependent platelet adhesion were reversed by exo

77 bodies against glycoprotein (GP) IIb-IIIa or GPIb-IX and occasionally against GPIa-IIa or GPV.

78 , the ligand-binding subunit of the platelet GPIb-IX complex and a marker for platelet senescence and

79 unctionally dominant subunit of the platelet GPIb-IX-V receptor complex, with the von Willebrand fact

80 mannin, high enough to inhibit MLCK, prevent GPIb-IX centralization.

81 connects the Von Willebrand factor receptor GPIb-IX-V to the underlying cytoskeleton in platelets.

82 orylation at Ser(609) of GPIbalpha regulates GPIb-IX interaction with 14-3-3 and may play important r

83 Following thrombin stimulation, GPIb-IX shifts from the membrane skeleton of the resting

84 The involvement of myosin II implies that GPIb-IX/ABP-280 complexes, linked to actin filaments, ar

85 binding to alpha(IIb)beta(3) indicating that GPIb-IX mediates a cellular signal leading to alpha(IIb)

86 We show that GPIb-IX-induced platelet aggregation and stable adhesion

87 Here we show that GPIb-IX-mediated activation of integrin alpha(IIb)beta(3

88 Because the GPIb-IX-V complex plays a part in regulating hemostasis

89 It remains unclear how the GPIb-IX-V complex is assembled and whether there is a ro

90 Akt1 and Akt2 are both required only in the GPIb-IX-mediated integrin activation (inside-out signali

91 ellular calcium; and (iv) independent of the GPIb-IX and GPIIb-IIIa complexes.

92 Mutagenesis of the GPIb-IX complex, which contains GPIbalpha, GPIbbeta, and

93 a decrease in the surface expression of the GPIb-IX complex, which is redistributed from the platele

94 we identify the platelet GPIX subunit of the GPIb-IX-V complex as an obligate and novel client of gp9

95 nt study, we report that the assembly of the GPIb-IX-V complex depends critically on a molecular chap

96 alpha is an integral membrane protein of the GPIb-IX-V complex found on the platelet surface that int

97 Here, we evaluated the role of the GPIb-IX-V complex in the transmission of cytoskeletal fo

98 Loss of the GPIb-IX-V complex is pathogenic for Bernard-soulier Synd

99 GPIb alpha, a glycoprotein component of the GPIb-IX-V complex, serves as a platelet membrane recepto

100 ith increased platelet surface levels of the GPIb-IX-V receptor complex.

101 In resting platelets, the GPIb-IX complex, the receptor for the von Willebrand fac

102 Thus, the GPIb-IX-V/VWF bond is able to transmit force, and uses t

103 SZ-2) that disrupts factor XI binding to the GPIb-IX-V complex also disrupted factor XI-raft associat

104 letal forces were transmitted to VWF through GPIb-IX-V, an unexpected finding given the widely held n

105 Thus, GPIb-IX-dependent platelet adhesion is doubly controlled

106 ctivation pathway in which ligand binding to GPIb-IX activates PKG that stimulates MAPK pathway, lead

107 vWF binding to GPIb-IX also activates soluble fibrinogen binding to alp

108 Ser(166) negatively regulates VWF binding to GPIb-IX and is one of the mechanisms by which PKA mediat

109 a (residues 202-231) required for binding to GPIb-IX complex and to the cytoplasmic domain of GPIbalp

110 Furthermore, vWF binding to GPIb-IX induces phosphorylation of Thr-202/Tyr-204 of ex

111 Thus, 14-3-3 binding to GPIb-IX is important in GPIb-IX signaling.

112 Thus, vWF binding to GPIb-IX is negatively regulated by the filamin-associate

113 phorylation and also enhanced VWF binding to GPIb-IX.

114 ffects of prostaglandin E1 on vWF binding to GPIb-IX.

115 alpha is important for 14-3-3zeta binding to GPIb-IX.

116 he 14-3-3zeta binds to recombinant wild type GPIb-IX but not to the GPIb-alpha mutants lacking C-term

117 Treatment of CHO cells expressing wild type GPIb-IX with a PKA inhibitor, PKI, reduced Ser(166) phos

118 VWF-binding function compared with wild type GPIb-IX.

119 actin also enhances vWF binding to wild type GPIb-IX.

120 Glycoprotein Ib-IX-V (GPIb-IX-V) mediates platelet tethering to von Willebrand

121 demonstrate an important role for Lyn in VWF/GPIb-IX-induced integrin activation mediated via the cGM

122 attributed to a selective inhibition in VWF/GPIb-IX-induced phosphorylation of cytosolic phospholipa

123 keleton is complete within 1 minute, whereas GPIb-IX centralization requires 5 to 10 minutes for comp

124 suggest that the signaling pathways by which GPIb-IX induces alpha(IIb)beta(3) activation are differe

125 tion occurred even in cells transfected with GPIb-IX lacking the domain on GPIbalpha that binds 14-3-