acvr1

Type

Gene1

Effect

Gene2

Sentence

Perturbation methods

Time of Interaction in evidence

territories of interaction or Tissue

Evidence for Direct

Authors

Journal

PubYear

Volume

Pages

MedLine Reference

Connectivity

# of References

Found In Pathways

Journal Link

Journal Reference

Mechanism

URN

ISSN

Issue

LocatorString

MedlineTA

PubMonth

p-value [Evol. Bioinformatics 2007:3(197)]

TextPath

Title

Expression

acvr1

positive

bmp2a

Since Bmps act as negative regulators of chordin expression (Schulte-Merker et al., 1998), and CA and KM Alk8 affect the expression of bmps2b and -4, it is expected that chordin expression would also be affected.

Zebrafish_Bmp2b_20080727

urn:agi-Expression:inout-urn:agi-llid:90:out-urn:agi-llid:650::positive

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=11165484&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0925477300005414

Expression

acvr1

positive

bmp2b

injected mRNA encoding a constitutively active version of Alk8 can rescue the strong dorsalization of bmp2b/swirl mutants.

overexpression

4.66

blastoderm

Hammerschmidt, M.

Development

2001

128

849

Regulation

acvr1

positive

bmp4

A constitutively active Alk8-TGFbeta-receptor can ectopically induce bmp2b and bmp4 and rescues the dorsalization of MZspg.

16775002:9

Zebrafish_gsc _20080801

urn:agi-Regulation:inout-urn:agi-llid:90:out-urn:agi-llid:652::positive

Expression

acvr1

neutral

bmp4

Together, these results show that Mrdr and alk8 strongly interact to positively regulate the onset of bmp2b/4 expression.

Zebrafish_gdf6a_07302008

urn:agi-Expression:inout-urn:agi-llid:90:out-urn:agi-llid:652::unknown

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3494&itool=AbstractPlus-nondef&uid=12601179&db=pubmed&url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12601179

Expression

acvr1

positive

bmp4

This indicates that pou2 acts upstream of Alk8, a maternally provided receptor implicated in the activation of zygotic bmp2b and bmp4 transcription.

PNAS

16775002:10

AllGenes-Pathway

http://www.pnas.org/cgi/content/full/100/6/3315

v100 i6 p3315

urn:agi-Expression:inout-urn:agi-llid:90:out-urn:agi-llid:652::positive

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=11165484&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0925477300005414

Expression

acvr1

negative

bmp4

In contrast, KM Alk8 down regulates ventral bmp2b expression in shield stage embryos (data not shown).

Zebrafish_Bmp2b_20080727

urn:agi-Expression:inout-urn:agi-llid:90:out-urn:agi-llid:652::negative

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=11165484&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0925477300005414

Expression

acvr1

positive

bmp7

injected mRNA encoding a constitutively active version of Alk8 can rescue the strong dorsalization of bmp7/snailhouse mutants

overexpression

4.66

blastoderm

Hammerschmidt, M.

Development

2001

128

849

Binding

acvr1

neutral

bmp7

OP-1 bound to ALK-2 and ALK-6 efficiently, and to ALK-3 less efficiently, whereas BMP-4 bound to ALK-3 and ALK-6 efficiently.

bone

Endocrinology

8006002:6

BMPR2-acvr1

http://endo.endojournals.org/cgi/content/full/143/4/1423

v143 i4 p1423

urn:agi-Binding:inout-urn:agi-llid:90:inout-urn:agi-llid:655:

digtext:http://dev.biologists.org/cgi/reprint/128/6/849.pdf

url(http%3a//dev.biologists.org/cgi/reprint/128/6/849.pdf):pdf

Regulation

acvr1

positive

bre

Furthermore, Smad7 inhibited the expression of the BMP-responsive reporter BRE-Luc (18) induced by the constitutively active forms of BMPRIA, BMPRIB, acvrl1, and ALK2 (Fig. 1B).

Zebrafish_smad2_20080729

urn:agi-Regulation:inout-urn:agi-llid:90:out-urn:agi-llid:9577::positive

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3494&itool=AbstractPlus-nondef&uid=17438144&db=pubmed&url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17438144

Expression

acvr1

neutral

bre

Furthermore, Smad7 inhibited the expression of the BMP-responsive reporter BRE-Luc (18) induced by the constitutively active forms of BMPRIA, BMPRIB, acvrl1, and ALK2 (Fig. 1B).

Zebrafish_smad2_20080729

urn:agi-Expression:inout-urn:agi-llid:90:out-urn:agi-llid:9577::unknown

Expression

acvr1

positive

bre

Furthermore, Smad7 inhibited the expression of the BMP-responsive reporter BRE-Luc (18) induced by the constitutively active forms of BMPRIA, BMPRIB, acvrl1, and ALK2 (Fig. 1B).

Zebrafish_smad2_20080729

urn:agi-Expression:inout-urn:agi-llid:90:out-urn:agi-llid:9577::positive

Expression

acvr1

neutral

chd

By early somite stages, CA Alk8 expressing embryos exhibit reduced chordin expression in diminished anterior neural structures and in the ventral tailbud (Fig. 2U,U').

Zebrafish_Bmp2b_20080727

urn:agi-Expression:inout-urn:agi-llid:90:out-urn:agi-llid:8646::unknown

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=11165484&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0925477300005414

Expression

acvr1

positive

chd

By early somite stages, CA Alk8 expressing embryos exhibit reduced chordin expression in diminished anterior neural structures and in the ventral tailbud (Fig. 2U,U').

Zebrafish_Bmp2b_20080727

urn:agi-Expression:inout-urn:agi-llid:90:out-urn:agi-llid:8646::positive

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=11165484&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0925477300005414

Expression

acvr1

negative

chd

Ectopic expression of CA Alk8 reduces chordin expression in shield and 80% epiboly stage embryos (Fig. 2O,R), while KM Alk8 expands chordin expression (Fig. 2M,P).

Zebrafish_Bmp2b_20080727

urn:agi-Expression:inout-urn:agi-llid:90:out-urn:agi-llid:8646::negative

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=11165484&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0925477300005414

Expression

acvr1

positive

dlx3b

in alk8 (a type I TGFbeta receptor) MO-injected embryos, vhnf1 expression in the endoderm is significantly reduced.

mutant embryos

ectoderm

Mary C. Mullins

Development

2001

128

859

Expression

acvr1

positive

foxa3

Decrease of Bmp activity by alk8 morpholino injection caused a change of foxa3 expression pattern.

Zebrafish_Chordin_20080727

urn:agi-Expression:inout-urn:agi-llid:90:out-urn:agi-llid:3171::positive

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=17217944&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0012-1606(06)01397-2

Expression

acvr1

negative

foxb1.2

the data suggest that Alk8 acts as a Bmp2b/7 receptor upstream of Smad5.

mutant embryos

ectoderm

Mary C. Mullins

Development

2001

128

859

Expression

acvr1

positive

gata2

the data suggest that Alk8 acts as a Bmp2b/7 receptor upstream of Smad5.

mutant embryos

ectoderm

Mary C. Mullins

Development

2001

128

859

Expression

acvr1

positive

hnf1b

Ved expression is up-regulated during gastrulation in MZ-laf/bmpRI signaling mutants.

MASO

gut

Lin, S.

Dev Biol

2007

303

561

Expression

acvr1

negative

ins

Embryos injected with alk8 morpholino exhibited remarkably reduced insulin expression (Fig. 8F).

Zebrafish_Chordin_20080727

urn:agi-Expression:inout-urn:agi-llid:90:out-urn:agi-llid:3630::negative

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=17217944&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0012-1606(06)01397-2

Expression

acvr1

neutral

myod1

KM Alk8 expression results in embryos exhibiting normal adaxial myoD expression along a broadened midline and thickened somitic myoD expression.

Zebrafish_Bmp2b_20080727

urn:agi-Expression:inout-urn:agi-llid:90:out-urn:agi-llid:4654::unknown

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=11165484&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0925477300005414

Expression

acvr1

positive

myod1

CA Alk8 expressing embryos often display an interrupted myoD expression pattern, where adaxial cells appaear fused, forming a loop toward the posterior end.

Zebrafish_Bmp2b_20080727

urn:agi-Expression:inout-urn:agi-llid:90:out-urn:agi-llid:4654::positive

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=11165484&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0925477300005414

Expression

acvr1

neutral

otx2

At 80% epiboly, CA Alk8 expressing embryos exhibit restricted dorsal anterior otx2 expression (Fig. 5C,C'), while KM Alk8 expressing embryos exhibit up regulated midline and lateral expansion of otx2 expression (Fig. 5A,A').

Zebrafish_Bmp2b_20080727

urn:agi-Expression:inout-urn:agi-llid:90:out-urn:agi-llid:5015::unknown

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=11165484&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0925477300005414

Expression

acvr1

positive

otx2

Zebrafish_Bmp2b_20080727

urn:agi-Expression:inout-urn:agi-llid:90:out-urn:agi-llid:5015::positive

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=11165484&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0925477300005414

Expression

acvr1

negative

otx2

Otx2 expression is reduced by CA Alk8 and expanded by KM Alk8, demonstrating a respective loss and expansion of prospective neural tissue that is appaarent at very early stages of development.

Zebrafish_Bmp2b_20080727

urn:agi-Expression:inout-urn:agi-llid:90:out-urn:agi-llid:5015::negative

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=11165484&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0925477300005414

ProtModification

acvr1

phosphorylation

smad1

B, in vitro phosphorylation of Smad1 by ALK2.

testis

Mol. Pharm

9748228:10235

AllGenes-Pathway

http://molpharm.aspetjournals.org/cgi/content/full/65/3/744

v65 i3 p744

phosphorylation

urn:agi-ProtModification:inout-urn:agi-llid:90:out-urn:agi-llid:4086::unknown:phosphorylation

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=11165484&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0925477300005414

ProtModification

acvr1

phosphorylation

smad1

The activated BMP type I receptors acvrl1, ALK2, ALK3 and ALK6 phosphorylate downstream target Smads 1/5/8 ([Heldin et al., 1997] and [Massague and Wotton, 2000]) which then bind to Smad4, migrate to the nucleus and regulate transcription of target genes

Zebrafish_bmp4_20080727

phosphorylation

urn:agi-ProtModification:inout-urn:agi-llid:90:out-urn:agi-llid:4086::unknown

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=18222420&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0012-1606(07)01565-5

Binding

acvr1

neutral

smad1

A, ALK2 interacts with Smad1.

Eur. J. Biochem

9748228:10229

Zebrafish_Bmp2b_20080727

http://www.ejbiochem.org/cgi/content/full/267/24/6954

v267 i24 p6954

urn:agi-Binding:inout-urn:agi-llid:90:inout-urn:agi-llid:4086:

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=11165484&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0925477300005414

Binding

acvr1

neutral

smad4

Evol. Bioinformatics

Zebrafish_bmp4_20080727

http://www.la-press.com/journals.php?pa=abstract&content_id=323

urn:agi-Binding:inout-urn:agi-llid:90:inout-urn:agi-llid:4089:

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=18222420&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0012-1606(07)01565-5

0.4800

Expression

acvr1

positive

smad5

In most MZ-laf/alk8 mutants dlx3 expression is absent.

MASO

4.66

blastoderm

1, 2

Hammerschmidt, M.

Development

2001

128

849

ProtModification

acvr1

phosphorylation

smad5

When stimulated by Bmp7, Alk2 recognizes and phosphorylates Smad1, and also phosphorylates Smad5 and Smad8 ( Macias-Silva et al., 1998).

Zebrafish_Bmp2b_20080727

phosphorylation

urn:agi-ProtModification:inout-urn:agi-llid:90:out-urn:agi-llid:4090::unknown

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=11165484&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0925477300005414

Expression

acvr1

positive

smad5

The ability of sbn/Smad5 mutants to block the ventralizing activities of CA alk8 demonstrate that alk8 functions upstream of the Smad5 transcription factor, and suggests that Smad5 is required in alk8 signaling pathways.

Zebrafish_Bmp2b_20080727

urn:agi-Expression:inout-urn:agi-llid:90:out-urn:agi-llid:4090::positive

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=11165484&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0925477300005414

ProtModification

acvr1

phosphorylation

smad8

Constitutively active BMP type I receptors, ALK-3 and ALK-6, as well as ALK-2, were phosphorylated Smad8 and induced Smad8 interaction with Smad4.

egg

Mol. Cell. Biol

10814522:3

BMPR2-acvr1

http://www.jbc.org/cgi/content/full/273/40/25628

v273 i40 p25628 (1998)

phosphorylation

urn:agi-ProtModification:inout-urn:agi-llid:90:out-urn:agi-llid:4093::unknown

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=11165484&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0925477300005414

Binding

acvr1

neutral

smurf2

In addition, Smurf1 associates with transforming growth factor-beta type I receptor through the inhibitory Smad (I-Smad) Smad7 and induces their degradation.

bone

Mol. Cell. Biol

12857866:1

Zebrafish_smad2_20080729

http://mcb.asm.org/cgi/content/full/25/4/1475

v25 i4 p1475

urn:agi-Binding:inout-urn:agi-llid:90:inout-urn:agi-llid:57154:

Expression

acvr1

positive

spi1

Ved expression is up-regulated during gastrulation in MZ-laf/bmpRI signaling mutants.

mutant embryos

11.66

lateral plate mesoderm

Lieschke, G. J.

Curr Biol

2006

506

Binding

acvr1

neutral

tgfb1

When coexpressed with the type II receptors of TGF-eta and activin, ALK-2 was shown to be able to form a heteromeric complex with TGF-eta and activin, respectively ( 7-9 ).

PNAS

9371779:10208

Zebrafish_Bmp2b_20080727

http://www.pnas.org/cgi/content/full/94/24/12938

v94 i24 p12938

urn:agi-Binding:inout-urn:agi-llid:90:inout-urn:agi-llid:7040:

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=11165484&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0925477300005414

Expression

acvr1

negative

ved

Foxb1.2 expression is expanded ventrally in MZ-laf embryos at 70% epiboly, the expansion is more pronounced in more vegetal regions.

mutant embryos

4.66

blastoderm

Franco Cotelli

Developmental Dynamics

2004

230

494

Regulation

bmp7

positive

acvr1

OP-1 alone increased ActR-I, BMPR-IA, and BMPR-II mRNA levels, but did not change the BMPR-IB level.

Endocrinology

9322928:10188

Zebrafish_Bmp2b_20080727

http://endo.endojournals.org/cgi/content/full/138/10/4181

v138 i10 p4181

urn:agi-Regulation:inout-urn:agi-llid:655:out-urn:agi-llid:90::positive

digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=11165484&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0925477300005414

Regulation

smad7

negative

acvr1

Thus, Smad7 preferentially blocked ActR-I signaling but had minimal effects on ActR-IB signaling.

Blood

10828018:10152

Zebrafish_smad2_20080729

http://www.bloodjournal.org/cgi/content/full/95/11/3371

v95 i11 p3371

urn:agi-Regulation:inout-urn:agi-llid:4092:out-urn:agi-llid:90::negative