ライフサイエンスコーパス: BMP-1

1 BMP-1 affects morphogenesis, at least partly, via biosyn

2 BMP-1 and mTLL-1 are shown to cleave Chordin, at sites s

3 BMP-1 application paired with a single serotonin (5HT) p

4 BMP-1 is also related to the product of the Drosophila p

5 BMP-1 lacking CUB glycosylation was translocated to the

6 BMP-1 molecules lacking any one of the CUB-specific glyc

7 BMP-1 molecules lacking individual glycosylation sites w

8 BMP-1 stimulates the conversion of newly secreted proapo

9 BMP-1, however, differed from other BMPs in that it its

10 BMP-1-related proteases mammalian Tolloid and mammalian

11 BMP-1/tolloid-like proteinases (BTPs) are major enzymes

12 BI-1 (BMP-1 isoenzyme inhibitor-1), a selective inhibitor of a

13 Vertebrate bone morphogenetic protein 1 (BMP-1) and Drosophila Tolloid (TLD) are prototypes of a

14 Bone morphogenetic protein 1 (BMP-1) and mammalian Tolloid (mTLD), two proteinases enc

15 C-proteinases: bone morphogenetic protein 1 (BMP-1) and mammalian Tolloid (mTLD).

16 alloproteinase bone morphogenetic protein 1 (BMP-1) is involved in endotrophin release and determined

17 which includes bone morphogenetic protein 1 (BMP-1), mammalian Tolloid (mTLD), mammalian Tolloid-like

18 Bone morphogenetic protein 1 (BMP-1), which is a tolloid member of the astacin-like fa

19 ide proteinase bone morphogenetic protein 1 (BMP-1).

20 gene encoding bone morphogenetic protein 1 (BMP-1).

21 Bone morphogenetic protein-1 (BMP-1) also plays key roles in regulating vertebrate mat

22 tant proteases bone morphogenetic protein-1 (BMP-1) and Drosophila Tolloid.

23 Bone morphogenetic protein-1 (BMP-1) is a metalloprotease that plays important roles i

24 Bone morphogenetic protein-1 (BMP-1) is a metalloprotease that plays key roles in regu

25 Bone morphogenetic protein-1 (BMP-1) plays key roles in regulating the deposition of v

26 Bone morphogenic protein-1 (BMP-1) was originally identified as one of several BMPs

27 alloproteinase bone morphogenetic protein-1 (BMP-1), a key regulator of extracellular matrix assembly

28 Bone morphogenetic protein-1 (BMP-1), a metalloprotease isolated from osteogenic extra

29 rocollagens by bone morphogenetic protein-1 (BMP-1), also known as type I procollagen C-proteinase ()

30 alloproteinase bone morphogenetic protein-1 (BMP-1), and for a gene encoding the closely related meta

31 of the family: bone morphogenetic protein-1 (BMP-1), mammalian tolloid (mTLD), tolloid-like (TLL)-1 a

32 -propeptide by bone morphogenetic protein-1 (BMP-1).

33 loid and human bone morphogenetic protein-1 (BMP-1).

34 endoproteinase/bone morphogenetic protein-1 (BMP-1).

35 nases, such as bone morphogenetic protein-1 (BMP-1).

36 enzymes of the bone morphogenetic protein-1 (BMP-1)/Tolloid family of metalloproteases that cleave LG

37 Bone morphogenetic protein-1 (BMP-1)/Tolloid-like metalloproteinases play key roles in

38 The mammalian bone morphogenetic protein-1 (BMP-1)/Tolloid-related metalloproteinases play key roles

39 ivation by the Bone morphogenetic protein-1 (BMP-1/Tolloid) metalloprotease, which occurs specificall

40 Studies with recombinant BMP-1, BMP-1 antibody, and BMP-1 siRNA establish this proteinas

41 In a proteinase survey, all BMP-1 isoenzymes processed human laminin-5 gamma2 and al

42 with recombinant BMP-1, BMP-1 antibody, and BMP-1 siRNA establish this proteinase as the major or on

43 In solution, BMP-1-FN interactions and BMP-1 cleavage of procollagen I were both enhanced by th

44 Both tolloid and BMP-1 encode metalloproteases that might activate TGF-be

45 n) was enhanced by PCPE-1 but not as well as BMP-1 retaining the CUB3 domain.

46 e used these differences in activity between BMP-1 and mTLL-2 to narrow in on the domains in BMP-1 th

47 s null for the Bmp1 gene, which encodes both BMP-1 and mammalian Tolloid, produce predominantly unpro

48 rate of procollagen cleavage by matrix-bound BMP-1.

49 m of the propeptide resistant to cleavage by BMP-1/TLD proteinases can cause significant increases in

50 alpha3 is also cleaved by BMP-1 in vitro, but the cleavage site is yet to be deter

51 -terminal sequences of products generated by BMP-1 cleavage of DMP1 match those predicted from proces

52 pro-alpha2(V) C-propeptides are processed by BMP-1-like enzymes, and pro-alpha1(V) C-propeptides are

53 sis, and that processing of the prodomain by BMP-1 potentiates the ability of OGN to modulate the for

54 otrimers, the processing of pro-alpha3(V) by BMP-1 occurs at an unexpected site within NH2-terminal g

55 (mTLL)-1 and -2 are two genetically distinct BMP-1-related proteinases, and mTLL-1 has been shown to

56 In the shorter form, pCP-1 (i.e., BMP-1), the sequence ends after the CUB3-domain.

57 On the other hand, inhibition of endogenous BMP-1 activity blocked the induction of two-trial LTF.

58 many bone morphogenetic proteins-especially BMP-1, -3, and -4-to confer osteoinductivity upon these

59 endotrophin release and determined the exact BMP-1 cleavage site.

60 oinductive because (1) they uniquely express BMP-1, (2) they express an appropriate combination of in

61 s redefining the specificity of cleavage for BMP-1-like enzymes.

62 As previously demonstrated for BMP-1 and mTLD, mTLL-1 is shown to specifically process

63 Saos-2 cells expressed mRNA for BMP-1, -2, -3, -4,-6, and TGF-beta 1.

64 Thus, a further role for BMP-1-Tolloid-like proteinases in formation of mineraliz

65 However, in vivo evidence of roles for BMP-1 and mTLL-1 in BMP signaling in mammals is lacking.

66 lpha3 and gamma2 chains to be substrates for BMP-1 in vitro.

67 es alternatively spliced RNA transcripts for BMP-1 and for a second longer protein, designated mammal

68 ises a metalloproteinase domain (either from BMP-1 or from mTLL-2) and the CUB1 domain of BMP-1 (the

69 ort the use of a cDNA library, prepared from BMP-1/mTld-null mouse embryos, to isolate cDNA clones fo

70 alian sFRP-1, -2, and -4 do not modify human BMP-1 activity on several of its known substrates includ

71 ppears as a tight binding inhibitor of human BMP-1, with a K(i) of 1.5 +/- 0.5 nM, and is shown to st

72 t the same site as the previously identified BMP-1 cleavage site.

73 ontrast to its action on procollagens I-III, BMP-1 does not cleave the C-propeptide of pro-alpha1(V)

74 with either of the corresponding domains in BMP-1 and mTLL-2 did not result in procollagen cleavage

75 -1 and mTLL-2 to narrow in on the domains in BMP-1 that specify PCP and chordinase activity.

76 part of the innate immune response, inhibits BMP-1 activity and blocks the maturation of proapo A1.

77 Tll1 double null mouse embryos, thus lacking BMP-1/mTLD, mTLL-1, or all three enzymes, respectively,

78 r genes encoding three of the four mammalian BMP-1/Tolloid-like proteinases appear to be deficient in

79 sed to varying extents by all four mammalian BMP-1/Tolloid-like proteinases, to generate a 27-kDa spe

80 d, to varying extents, by all four mammalian BMP-1/Tolloid-like proteinases, to generate fragments si

81 r genes encoding three of the four mammalian BMP-1/Tolloid-related proteinases produce only unprocess

82 pression domains of all four known mammalian BMP-1/TLD-like proteases [BMP-1, mammalian Tolloid (mTLD

83 oids, but truncated forms of TLL-2 mimicking BMP-1 are unable to cleave chordin.

84 n differences in the activities of monomeric BMP-1 and dimers of mTLD and TLL-1.

85 In addition, mTLD/BMP-1 null mice were shown to have deficient laminin-5 p

86 mp1 gene, which encodes variants of the mTLD/BMP-1 metalloproteases, as a critical regulator of alpha

87 h reduced laminin-gamma2 processing via mTLD/BMP-1.

88 LTF, whereas neither a single 5HT pulse nor BMP-1 alone effectively did so.

89 that PCPE-1 had no effect on the ability of BMP-1 to cleave chordin.

90 Thus, the combination of BMP-1/mTLD and mTLL-1 is shown to be responsible for the

91 BMP-1 or from mTLL-2) and the CUB1 domain of BMP-1 (the CUB1 domain of mTLL-2 cannot substitute for t

92 ollagen, but in addition, the CUB3 domain of BMP-1 appears to augment the interaction.

93 L-2 cannot substitute for the CUB1 domain of BMP-1).

94 it acts directly on the catalytic domain of BMP-1.

95 ave chordin if coupled to the CUB1 domain of BMP-1.

96 1) the metalloproteinase and CUB2 domains of BMP-1 are absolutely required for PCP activity; swaps wi

97 he glycosylation sites in the CUB domains of BMP-1 are important for secretion and stability of the m

98 atal, and adult brain in which expression of BMP-1 and mTld has not been observed.

99 cyte cultures but little or no expression of BMP-1, mTLL-1, or mTLL-2.

100 edundancy obscuring the in vivo functions of BMP-1-related proteases in mammals, we here characterize

101 s likely to be involved in the inhibition of BMP-1 activity by Szl.

102 as well as TGF-beta 1 mRNA, while levels of BMP-1 and BMP-3 mRNA were either not detectable or detec

103 sacrcoma cells, TGF-beta1 elevated levels of BMP-1 mRNA approximately 7-fold and elevated levels of m

104 The unexpectedly large number of BMP-1/TLD-like protease genes (23) results primarily fro

105 The presence of BMP-1 and -4 protein was confirmed in Saos-2 cells by im

106 To more directly assess the roles of BMP-1 and mTLL-1 in lysyl oxidase activation by connecti

107 When compared with known structures of BMP-1 in complex with small molecule inhibitors, this re

108 of PCPE mRNA is shown to differ from that of BMP-1 and type I procollagen during mouse development, c

109 dependent manner and that, like procollagen, BMP-1 colocalizes with FN fibrils in the matrix microenv

110 ur known mammalian BMP-1/TLD-like proteases [BMP-1, mammalian Tolloid (mTLD), mammalian Tolloid-like

111 d that the minimal procollagen C-proteinase (BMP-1 lacking the EGF and CUB3 domain) was enhanced by P

112 e NC2 domain by the procollagen C-proteinase/BMP-1 in dimer assembly.

113 Recombinant BMP-1 cleaves gamma2 in vitro, both within intact lamini

114 Recombinant BMP-1 molecules lacking all glycosylation sites or the t

115 Studies with recombinant BMP-1, BMP-1 antibody, and BMP-1 siRNA establish this pr

116 ons and were induced by TGF-beta1 to secrete BMP-1 and mTld predominantly as unprocessed proenzymes.

117 Secreted BMP-1 and mTld, induced by TGF-beta1 in MG-63 and other

118 up-regulated by TGF-beta1 and that secreted BMP-1, induced by TGF-beta1, is either processed to an a

119 In vitro studies have shown BMP-1 and mTLL-1 capable of cleaving Chordin, an extrace

120 Instead, the single BMP-1-specific cleavage site within pro-alpha1(V) chains

121 In solution, BMP-1-FN interactions and BMP-1 cleavage of procollagen

122 ession domains of the four proteases suggest BMP-1 as the major Chordin antagonist in early mammalian

123 strated developmental roles in other systems-BMP-1/TLD (tolloid) (astacins), MMPs (matrix metalloprot

124 e at the correct physiological site but that BMP-1 is 3-, 15-, and 20-fold more efficient than mTLL-1

125 We found that BMP-1 binds to a cell-assembled ECM in a dose-dependent

126 Here, we show that BMP-1 cleaves probiglycan at a single site, removing the

127 Here we show that BMP-1 is itself up-regulated by TGF-beta1 and that secre

128 This further suggests that BMP-1 activity facilitates basement membrane assembly, b

129 Sequence analysis suggests that BMP-1 has six potential N-linked glycosylation sites (i.

130 The BMP-1/Tolloid family of metalloproteases is thereby impl

131 Three proteins-Chordin, Twsg, and the BMP-1 protease-successfully displaced gradients by shutt

132 ap extensively that previously shown for the BMP-1 and mTld RNA forms.

133 Consistent with possible roles for the BMP-1/Tolloid-like proteinases in the physiological proc

134 rventricular septum, where expression of the BMP-1 gene, Bmp1, was not observed.

135 mmunoblot and quantitative PCR survey of the BMP-1 isoenzymes revealed expression of mTLD in primary

136 ferent chromosomal location than that of the BMP-1/mTld gene.

137 gs raise the possibility that members of the BMP-1/TLD family may be involved in activating latent my

138 Here, we report that the BMP-1/Tolloid family metalloprotease Tolkin (Tok) is res

139 Therefore, BMP-1 was a member of the "astacin families" of zinc-req

140 hat procollagen C-proteinase is identical to BMP-1.

141 lloid, a putative metalloprotease related to BMP-1, enhances DPP function, while SOG, an ortholog of

142 ditional proteinases structurally similar to BMP-1 and mTLD: the genetically distinct mammalian Tollo

143 of the bone morphogenetic protein-1/tolloid (BMP-1/TLD) family of metalloproteinases can cleave the m

144 Aplysia tolloid/BMP-1-like protein (apTBL-1) might regulate the morpholo

145 he interactions of Complement C1r/C1s, Uegf, BMP-1 (CUB) domain-containing proteins in diverse biolog

146 related to Drosophila tolloid and vertebrate BMP-1 (Reynolds et al., Development 114, 769-786).

147 ction may be mediated, at least in part, via BMP-1 by this novel mechanism.