ライフサイエンスコーパス: JAK kinase

1 ypes identical to mutations in the Hopscotch/JAK kinase.

2 eceptor (IL-6R) also activates STAT3 through Jak kinase.

3 response to activation of the Drosophila Hop Jak kinase.

4 interaction of some cytokine receptors with Jak kinases.

5 e cytokine family of receptors that activate JAK kinases.

6 nt with activation of JAK2 in trans by other JAK kinases.

7 ved in tyrosine kinases and may be unique to Jak kinases.

8 uitment, and activation of the intracellular JAK kinases.

9 d activate certain STAT proteins, in lieu of JAK kinases.

10 s may be the primary functional attribute of JAK kinases.

11 cers and activators of transcription) by the Jak kinases.

12 eract with and form signaling complexes with Jak kinases.

13 but not on the enzymatic activity of Src or Jak kinases.

14 ssociated with a corresponding activation of JAK kinases.

15 res activation of receptor-associated Janus (Jak) kinases.

16 with imatinib together with an inhibitor of JAK kinases abrogates this resistance, suggesting that t

17 IRAK1 phosphorylation, NF-kappaB signalling, JAK kinase activation of STAT3, and secretion of IL-6, I

18 resulted in recovered JAK-STAT3 binding and JAK kinase activity after an initial reduction, although

19 SOCS-1 is a potent inhibitor of Jak kinase activity and of signaling initiated by severa

20 diated through altered JAK-STAT3 binding and JAK kinase activity and that this compensatory pathway a

21 In summary, optimal JAK kinase activity is a critical determinant of normal

22 JAK kinase activity is regulated by the adjacent pseudok

23 Inhibition of Jak kinase activity with Jak inhibitor I completely reve

24 Aberrations in JAK kinase activity, that may lead to derailment of one

25 IL-2 signaling that functions by inhibiting Jak kinase activity.

26 ly had B-cell development/differentiation or JAK kinase alterations but had a high frequency (62%) of

27 es identical to those in the hopscotch (hop)/JAK kinase and marelle (mrl)/Stat92e mutations.

28 Agonist antiserum to TNFR1 induced Jak kinase and STAT protein phosphorylation.

29 rowth factor-beta and its signaling pathway (JAK kinase and STAT-6, Smad2/3, and Smad7) appear to pla

30 enotypes identical to those in the Hopscotch/JAK kinase and stat92E/STAT mutations.

31 ferons (IFNs) bind surface receptors, induce JAK kinases and activate STAT transcription factors to s

32 kinase signaling through SRC family-TNK2 or JAK kinases and differential sensitivity to kinase inhib

33 IL-6 induced phosphorylation of JAK kinases and gp130, regardless of the proliferative r

34 glioblastoma by downregulating expression of JAK kinases and inhibiting activation of STAT3.

35 regulation of cytokine-induced activation of Jak kinases and STAT transcription factors.

36 hich IFNaR1 mediates the interaction between JAK kinases and the STAT transcription factors.

37 ma, as determined by a lack of activation of jak kinases and the transcription factor, STAT1(alpha),

38 rosine phosphorylation of its receptors, two JAK kinases and three STAT transcription factors.

39 ss the phenotype of the hyperactive hopTum-1 Jak kinase, and recovered a mutation that meiotically ma

40 activation of CRLF2 expression, mutation of JAK kinases, and alterations of IKZF1 cooperate to promo

41 activation of Stat3 via the FGF receptor and JAK kinases, and pharmacological inhibition of MEK toget

42 ylation, TSLP was reported to not signal via JAK kinases, and the mechanism by which TSLP regulates S

43 less, a cytokine-like receptor; Hopscotch, a JAK kinase; and Stat92E, a STAT transcription factor.

44 In addition, JAK kinases appear to be essential for the phosphorylati

45 Our results show that none of the JAK kinases are constitutively phosphorylated by v-src o

46 Jak kinases are critical signaling components in hematop

47 Although Jak kinases are essential for initiating cytokine signal

48 and suggest targeting pre-BCR signaling and JAK kinases as potential therapeutic strategies.

49 istinct classes of cytokine receptors engage Jak kinases as primary effectors.

50 a type I cytokine receptor are important for Jak kinase association but also suggest that two IL-2Rbe

51 phorylation of STAT3 in MM cells by reducing Jak kinase autophosphorylation, and leads to down-regula

52 These findings establish that JAK kinase binding to betac requires the presence of thr

53 Furthermore, inhibition of Jak kinases by TGF-beta was associated with a decrease i

54 Activation of Jak kinases by TNF was associated with tyrosine phosphor

55 the dominant hop(Tum-l) mutation in the Hop Jak kinase causes leukemia-like and other developmental

56 mphoma B-cell line, expressed the four known Jak kinases constitutively tyrosine phosphorylated, with

57 need for development of better therapies for JAK kinase-dependent malignancies.

58 or (EpoR) mutants, we have demonstrated that Jak kinase-dependent signals initiated from the membrane

59 The Jak kinases exhibit distinct cytokine receptor associati

60 Although Jak2 and other Jak kinase family members are phosphorylated on numerous

61 lines driven by similar fusions of the other JAK kinase family members.

62 We show that Jak2 is the requisite Jak kinase for signaling by the LRb intracellular domain

63 In contrast, loss of JAK kinase function has been found to result in disease

64 t of this hypothesis, it has been found that JAK kinase function is required for optimal activation o

65 Evidence to date, indicates that JAK kinase function may integrate components of diverse

66 Thus, over-activation of JAK kinases has been implicated in tumorigenesis.

67 stitutively activated form of the Drosophila JAK kinase (hop(Tum-l)) promotes Madm nuclear translocat

68 loss of function mutations in the Drosophila Jak kinase Hopscotch (Hop) to determine the role of Hop

69 flies wild-type and mutant for Dcr-2 or the JAK kinase Hopscotch to infections by seven RNA or DNA v

70 We demonstrate that the JAK kinase, Hopscotch, and the STAT DNA-binding protein,

71 may be important to re-evaluate the role of Jak kinases in other cytokine signaling pathways as well

72 studies have been conducted on the roles of Jak kinases in the hematopoietic cells, much less is kno

73 Tyk2 kinase and the hyperphosphorylation of Jak kinases in the motheaten cells that lack functional

74 To identify the pathways downstream of Jak kinases in v-Abl-mediated signaling, we examined the

75 ions and lipid elevations have occurred with JAK-kinase inhibition.

76 JAK kinase inhibitors have depressed leukemic T cell lin

77 work has been dedicated to the discovery of JAK kinase inhibitors resulting in several compounds ent

78 f various solid tumors, including the use of JAK kinase inhibitors such as AZD1480.

79 itors of cytokine-receptor interactions, and JAK kinase inhibitors that may revolutionize therapy for

80 ed IL-9-mediated tyrosine phosphorylation of JAK kinases, insulin receptor substrate-2, and signal tr

81 ired IL-9-induced cell growth, activation of JAK kinases, insulin receptor substrate-2, and STAT3 and

82 ociation but also suggest that two IL-2Rbeta-Jak kinase interactions are important for IL-2 signaling

83 nd interleukin-3) and that activation of the Jak kinase is necessary and sufficient for these effects

84 Our results suggest that the N-terminus of Jak kinases is critical for receptor binding, and is the

85 ms by which Jak2, the cognate LRb-associated Jak kinase, is regulated and mediates downstream signali

86 y be an important function attributed to the JAK kinases, it is certainly not the only function perfo

87 (IFN-gammaR2), and causes activation of two Jak kinases (Jak1 and Jak2).

88 It is interesting to note that JAK kinases (JAK1, JAK2, JAK3, and Tyk2) were not consis

89 oR) requires only one receptor chain and one Jak kinase (Jak2).

90 zation mediates the trans-phosphorylation of Jak kinases, Jaks phosphorylate receptors at tyrosine si

91 and Y510, suggesting that the role for this Jak kinase may extend beyond the Jak-STAT pathway.

92 In such a scenario, JAK kinases may be more crucial to phosphorylation of th

93 e phosphorylation of STAT3 and suggests that Jak kinases may not be required in this cascade.

94 These data suggest that Jak kinases may play an important role in v-Abl induced

95 ciated with myeloid cell proliferation while JAK kinases mediate the activation of Erk-2 pathway whic

96 of these diverse signaling cues from active JAK kinases, members of the Src-family kinases and STAT

97 The concerted action of JAK kinases, members of the Src-kinase family and STAT p

98 of Bcl-XL protein levels is mediated by the Jak kinase pathway and is independent of other signaling

99 he target genes through which the Drosophila Jak kinase pathway regulates hemocyte development.

100 Signaling targets of Jak kinase pathways included members of the Bcl-2 family

101 dominant negative mutant vector at Tyr-701 (JAK kinase phosphorylation site) blocked the effect of I

102 However, mutations of Stat1 at Tyr-701 (JAK kinase phosphorylation site), Glu-428/429 (putative

103 n these cells, the v-Abl oncoprotein and the JAK kinases physically associate.

104 therefore likely to determine specificity of Jak kinase-receptor interactions.

105 The data support the concepts that Jak kinases regulate cell survival through their selecti

106 Jak/STAT signaling pathway, as inhibition of Jak kinases results in a loss of antiviral activity driv

107 on of multiple signaling cascades, involving Jak kinases, signal transducer and activator of transcri

108 Constitutive nuclear factor (NF)-kappaB and JAK kinase signalling promotes malignant cell survival i

109 ed the effects of dominant-negative forms of JAK kinases, STAT transcription factors, and Raf-1 in tr

110 Here, we describe the role of the IFN-Jak kinase-Stat (signal transducer and activator of tran

111 Jak kinase-Stat protein pathways play a critical role in

112 y IFNgamma, or pharmacological inhibition of JAKs, kinases that phosphorylate STATs, prevented the in

113 As SOCS-1 is a known potent inhibitor of Jak kinases, the mechanism by which v-Abl bypasses SOCS-

114 varying degrees of selectivity against other JAK kinases to address the requirement for TYK2 catalyti

115 SOCS-1 regulation to constitutively activate Jak kinases was investigated.

116 35S-labeled Jak kinases were precipitated from a cell-free system an

117 litinib is a small-molecule inhibitor of the JAK kinases, which has been approved for the treatment o

118 BCR-ABL also activates JAK kinases, which may provide a mechanism for STAT acti

119 Our results associate Pyk2 and Jak kinases with the linkage of signals emanating from c

120 nhance tumorigenesis induced by an oncogenic JAK kinase without affecting JAK/STAT signaling.