ライフサイエンスコーパス: u-PA

1 u-PA is 47-fold more active than t-PA for cleavage of a

2 ino terminal fragment of u-PA inhibited 125I-u-PA binding to platelets with a mean IC50 of 65 and 58

3 In contrast to resting platelets, 125I-u-PA did not bind to thrombin-induced platelets.

4 membrane and of U937 cell proteins with 125I-u-PA revealed a u-PA binding protein of approximately 70

5 A u-PA complex was further shown by enzyme-linked immunoso

6 U937 cell proteins with 125I-u-PA revealed a u-PA binding protein of approximately 70 kD in the plate

7 by receptor-bound urinary-type Pg activator (u-PA) and initiated a Ca(++) signaling cascade.

8 ent of urokinase-type plasminogen activator (u-PA) and PAI-1.

9 -PAR) binds urokinase plasminogen activator (u-PA) and participates in plasminogen activation in addi

10 activators urokinase plasminogen activator (u-PA) and tissue plasminogen activator (t-PA).

11 ation, urokinase-type plasminogen activator (u-PA) and u-PA receptor were observed in the immunopreci

12 genous urokinase-type plasminogen activator (u-PA) has been identified in platelet membrane, and plat

13 ity of urokinase-type plasminogen activator (u-PA) increases very rapidly (within 1 minute) after par

14 Human urokinase type plasminogen activator (u-PA) is a member of the chymotrypsin family of serine p

15 e that urokinase-type plasminogen activator (u-PA) is importantly involved in fibrinolysis, but its p

16 r (t-PA) or urokinase plasminogen activator (u-PA) levels, which remained unchanged.

17 binds urokinase-type plasminogen activator (u-PA) through specific interactions with uPAR domain 1,

18 LN endogenous urinary plasminogen activator (u-PA), as well as by added tissue Pg Activator (t-PA), s

19 A) and urokinase-type plasminogen activator (u-PA), by modifying the technique of substrate phage dis

20 PA) or urokinase-type plasminogen activator (u-PA).

21 otease urokinase-type plasminogen activator (u-PA).

22 gen (Plg) by either urokinase Plg activator (u-PA) or tissue Plg activator (t-PA).

23 ively, our data show that in culture, active u-PA is present and cleaves scHGF to tcHGF in the contex

24 membrane contains a specific, high affinity u-PA-binding protein that is distinct from u-PAR.

25 s using either a polyclonal antibody against u-PA or, since u-PA functions in the context of its rece

26 Both t-PA and u-PA hydrolyze the engineered proteins at the inserted t

27 Cleavage of proteins by t-PA and u-PA is sequence selective.

28 ibitor, antibodies directed against t-PA and u-PA, and epsilon-aminocaproic acid, a lysine analog tha

29 f the protease domains of two-chain t-PA and u-PA, and molecular modeling of the corresponding single

30 ary physiological inhibitor of both t-PA and u-PA, confirmed this prediction and indicated a predomin

31 nhibitor-1 (PAI-1), an inhibitor of t-PA and u-PA, in a rat model of aortic aneurysm.

32 kinase-type plasminogen activators (t-PA and u-PA, respectively), of their specific inhibitor (PAI-1)

33 a substrate to discriminate between t-PA and u-PA.

34 kinase-type plasminogen activator (u-PA) and u-PA receptor were observed in the immunoprecipitates of

35 the lungs of bleomycin-treated Pg(-)(/-) and u-PA(-)(/-) mice.

36 ts, we used inactive variants of trypsin and u-PA whose catalytic serine S195 had been replaced by al

37 lasminogen activation by platelet-associated u-PA was studied.

38 t-PA for cleavage of a sequence known to be u-PA selective within small peptide substrates, whereas

39 Because u-PA, t-PA, and plasmin have a limited proteolytic activ

40 or was similar to wild-type u-PAR in binding u-PA and initiating plasminogen activation.

41 the primary physiological inhibitor of both u-PA and t-PA, that inhibited u-PA approximately 70 time

42 To test whether the active, receptor-bound u-PA from the cell cultures was cleaving scHGF, iodinate

43 logical significance of receptor cleavage by u-PA, we engineered and expressed a two-chain urokinase

44 ved as much as 120 times more efficiently by u-PA than by tissue type plasminogen activator (t-PA), a

45 e cleaved 840-5300 times more efficiently by u-PA than peptides containing the physiological target s

46 investigated using recombinant, single chain u-PA.

47 r for u-PA and a portion of the single-chain u-PA (scu-PA) intrinsic to blood is tightly associated w

48 ves scu-PA to the mature protease, two-chain u-PA (tcu-PA), which is efficiently and irreversibly inh

49 These findings may help explain u-PA-mediated physiological fibrinolysis and have implic

50 a value of 9 for wild type t-PA and 250 for u-PA.

51 te PA activity in parallel with the mRNA for u-PA.

52 echanism, as they carry a novel receptor for u-PA and a portion of the single-chain u-PA (scu-PA) int

53 dine 144 of t-PA to an acidic residue, as in u-PA, selectively suppressed the activity of single-chai

54 se in PAI-1 and TF mRNAs and the decrease in u-PA mRNA in the kidneys of MRL lpr/lpr mice suggests th

55 nhibitor-1 RNA and protein and a decrease in u-PA RNA as noted by quantitative reverse transcriptase-

56 tion to these changes in PAI-1, decreases in u-PA mRNA and increases in TF mRNA were demonstrated in

57 Levels in u-PA(-)(/-) and u-PAR(-)(/-) mice were similar to those

58 ibitor of both u-PA and t-PA, that inhibited u-PA approximately 70 times more rapidly than it inhibit

59 stantially more PAI-1 and substantially less u-PA were present in the atherectomy samples from subjec

60 t membrane degradation through cell-mediated u-PA activation of Pg with possible involvement of matri

61 A mutant recombinant murine u-PA that retains receptor binding but not proteolytic a

62 ors cells secrete an inhibitor of the murine u-PA receptor.

63 Mutant u-PA and a reporter gene pRK luciferase were transfected

64 Several clones expressing mutant u-PA and luciferase were identified by Western blotting,

65 tional MAT-LyLu cell lines expressing mutant u-PA.

66 itory activity of PAI-1 against t-PA but not u-PA suggested that the mechanism of loop insertion is s

67 report, the mechanism of the association of u-PA with platelets was investigated using recombinant,

68 Complexion of u-PA with a platelet membrane protein was also shown by

69 eled u-PA and the amino terminal fragment of u-PA inhibited 125I-u-PA binding to platelets with a mea

70 ighly selective, high affinity inhibitors of u-PA and, consequently, may facilitate the development o

71 also shown by gel filtration of a mixture of u-PA and platelet membrane proteins.

72 It also suggests that modulation of u-PA activity by various growth factors is relevant for

73 Reactivation of u-PA was not due to the direct action of thrombin, but r

74 e-dependent (1 to 10 u/mL) partial return of u-PA activity.

75 this study to determine whether the role of u-PA in prostate cancer induced angiogenesis and seconda

76 In view of the well-recognized roles of u-PA as one of the major initiators of the matrix proteo

77 optimal subsite occupancy for substrates of u-PA.

78 were labile to selective cleavage by t-PA or u-PA when in the context of a peptide were introduced in

79 o the cell in the presence of either t-PA or u-PA, conversion to Lys-Pg was observed, but conversion

80 enhanced interstitial fibrosis in Pg(-)(/-), u-PA(-)(/-), and t-PA(-)(/-) mice relative to WT and u-P

81 omycin-treated WT mice and not in Pg(-)(/-), u-PA(-)(/-), and u-PAR(-)(/-) mice or saline controls.

82 ect is pronounced for the selective protease u-PA.

83 n platelets were incubated with radiolabeled u-PA, the u-PA was found to specifically and saturably b

84 a polyclonal antibody against u-PA or, since u-PA functions in the context of its receptor (u-PAR), a

85 These findings suggest that cell surface u-PA contributes to prostate cancer growth by enhancing

86 version to tc-u-PA and incorporation into tc-u-PA.PAI complexes) in an LRP/alpha2MR-dependent manner,

87 hoblasts by facilitating the clearance of tc-u-PA.PAI complexes and regeneration of unoccupied cell s

88 UK (primarily following its conversion to tc-u-PA and incorporation into tc-u-PA.PAI complexes) in an

89 nd complexes between two-chain urokinase (tc-u-PA) and plasminogen activator inhibitor type-1 (PAI-1)

90 e upon binding to its cellular cofactor, the u-PA receptor (u-PAR), hence activating an enzymatic cas

91 al or a polyclonal antibody specific for the u-PA cell-surface receptor (u- PAR), failed to show evid

92 s were incubated with radiolabeled u-PA, the u-PA was found to specifically and saturably bind to the

93 ent, the majority was of the urokinase type (u-PA) as determined by neutralization studies using eith

94 Unlabeled u-PA and the amino terminal fragment of u-PA inhibited 1

95 f t-PA, however, is not shared by urokinase (u-PA), a plasminogen activator that is very closely rela

96 plasminogen activators (including urokinase (u-PA), streptokinase (SK), and tissue plasminogen activa

97 e plasminogen activator (t-PA) or urokinase (u-PA) resulted in rapid decreases of fluorescence coinci

98 her tissue Pg activator (t-PA) or urokinase (u-PA) were compared when these Pg forms were either boun

99 ient for plasminogen (Pg(-)(/-)), urokinase (u-PA(-)(/-)), urokinase receptor (u-PAR(-)(/-)), or tiss

100 Binding of the serine protease urokinase (u-PA) to its receptor on tumor cell surfaces facilitates

101 n to take up exogenous high molecular weight u-PA from the ambient medium.

102 Similar results were obtained when u-PA was used as activator.

103 oportionate elevation of PAI-1 compared with u-PA observed in atheromatous material extracted from ve