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Field	Query

	Field	Term

General Information:

Id:	3,680
Organism:	Mus musculus
Strain:	C57BL/6 (B6-Ly5.2)/(B6-Ly5.1); Mx-1-Cre, 2 month-old; Tgfbr2flox/-Rag2-/- mice
Reference:	Yamazaki S et al.(2011) Nonmyelinating Schwann cells maintain hematopoietic stem cell hibernation in the bone marrow niche Cell 147: 1146-1158 [PMID: 22118468]

Interaction Information:

Comment	TGF-beta binds to its receptor composed of Tgf-betaRII and TGF-betaRI. [Method: cited information]
Formal Description Interaction-ID: 35281	gene/protein Tgfbr1 interacts (colocalizes) with gene/protein Tgfbr2 thereby forming an active Tgf-beta receptor
Drugbank entries	Show/Hide entries for Tgfbr1 or Tgfbr2
Drugbank DB03921	4-(3-Pyridin-2-Yl-1h-Pyrazol-4-Yl)Quinol ... not specified TGFBR1
Drugbank DB04434	Naphthyridine Inhibitor not specified TGFBR1
Drugbank DB04480	3-(4-Fluorophenyl)-2-(6-Methylpyridin-2- ... not specified TGFBR1
Drugbank DB07152	N-[4-(5-fluoro-6-methylpyridin-2-yl)-5-q ... not specified TGFBR1
Drugbank DB07267	2-(6-methylpyridin-2-yl)-N-pyridin-4-ylq ... not specified TGFBR1
Drugbank DB08450	N-1H-indazol-5-yl-2-(6-methylpyridin-2-y ... not specified TGFBR1
Drugbank DB04077	Glycerol not specified TGFBR2
Drugbank DB04077	Glycerol not specified TGFBR2

Comment	TGF-beta binds to its receptor composed of Tgf-betaRII and TGF-betaRI. [Method: cited information]
Formal Description Interaction-ID: 35282	complex/PPI Tgf-beta receptor increases_activity of process transforming growth factor beta receptor signaling pathway

Comment	TGF-beta binds to its receptor composed of Tgf-betaRII and TGF-betaRI. [Method: cited information]
Formal Description Interaction-ID: 35283	gene/protein Tgfbr1 is_part_of complex/PPI Tgf-beta receptor
Drugbank entries	Show/Hide entries for Tgfbr1
Drugbank DB03921	4-(3-Pyridin-2-Yl-1h-Pyrazol-4-Yl)Quinol ... not specified TGFBR1
Drugbank DB04434	Naphthyridine Inhibitor not specified TGFBR1
Drugbank DB04480	3-(4-Fluorophenyl)-2-(6-Methylpyridin-2- ... not specified TGFBR1
Drugbank DB07152	N-[4-(5-fluoro-6-methylpyridin-2-yl)-5-q ... not specified TGFBR1
Drugbank DB07267	2-(6-methylpyridin-2-yl)-N-pyridin-4-ylq ... not specified TGFBR1
Drugbank DB08450	N-1H-indazol-5-yl-2-(6-methylpyridin-2-y ... not specified TGFBR1

Comment	TGF-beta binds to its receptor composed of Tgf-betaRII and TGF-betaRI. [Method: cited information]
Formal Description Interaction-ID: 35284	gene/protein Tgfbr2 is_part_of complex/PPI Tgf-beta receptor
Drugbank entries	Show/Hide entries for Tgfbr2
Drugbank DB04077	Glycerol not specified TGFBR2
Drugbank DB04077	Glycerol not specified TGFBR2

Comment	Activated Tgf-beta receptor RI/RII phosphorylates Smad2 and 3. In HSC (CD150+CD48-CD41-Lin-) Smad2 and 3 are phosphorylated. [Method: BM section, FACS, fluorescence photomicrographs]
Formal Description Interaction-ID: 35285	complex/PPI Tgf-beta receptor increases_phosphorylation of gene/protein Smad2 in HSC (CD150+CD48-CD41-Lin-)
Drugbank entries	Show/Hide entries for Smad2
Drugbank DB04522	Phosphonoserine not specified SMAD2
Drugbank DB04522	Phosphonoserine not specified SMAD2

Comment	Activated Tgf-beta receptor RI/RII phosphorylates Smad2 and 3. In HSC (CD150+CD48-CD41-Lin-) Smad2 and 3 are phosphorylated. [Method: BM section, FACS, fluorescence photomicrographs]
Formal Description Interaction-ID: 35286	complex/PPI Tgf-beta receptor increases_phosphorylation of gene/protein Smad3 in HSC (CD150+CD48-CD41-Lin-)

Comment	Tgfbr2-deficient HSCs were associated with reduced p-Smad2/3, increased cycling, and reduced long-term repopulating activity in HSCs. These results demonstrated for the first time that TGF-beta/Smad signaling is active in BM HSCs and maintains their dormancy. [Method: Tgfbr2-deficient mice, BM section, FACS, fluorescence photomicrographs]
Formal Description Interaction-ID: 35287	gene/protein Tgfbr2 increases_activity of process SMAD protein signal transduction in HSC (CD34-KSL) in vivo
Drugbank entries	Show/Hide entries for Tgfbr2
Drugbank DB04077	Glycerol not specified TGFBR2
Drugbank DB04077	Glycerol not specified TGFBR2

Comment	Loss of Tgfbr2 was associated with reduced p-Smad2/3, increased cycling, and reduced long-term repopulating activity in HSCs. These results demonstrated for the first time that TGF-beta/Smad signaling is active in BM HSCs and maintains their dormancy. [Method: cell cycle analysis in Tgfbr2-deficient HSCs (CD34-KSL)]
Formal Description Interaction-ID: 35288	gene/protein Tgfbr2 decreases_activity of process cell cycle in HSC (CD34-KSL) in vivo
Drugbank entries	Show/Hide entries for Tgfbr2
Drugbank DB04077	Glycerol not specified TGFBR2
Drugbank DB04077	Glycerol not specified TGFBR2

Comment	Loss of Tgfbr2 was associated with reduced p-Smad2/3, increased cycling, and reduced long-term repopulating activity in HSCs. These results demonstrated for the first time that TGF-beta/Smad signaling is active in BM HSCs and maintains their dormancy. [Method: cell cycle analysis in Tgfbr2-deficient HSCs (CD34-KSL)]
Formal Description Interaction-ID: 35289	gene/protein Tgfbr2 increases_activity of process quiescence in HSC (CD34-KSL) in vivo
Drugbank entries	Show/Hide entries for Tgfbr2
Drugbank DB04077	Glycerol not specified TGFBR2
Drugbank DB04077	Glycerol not specified TGFBR2

Comment	Loss of Tgfbr2 was associated with reduced p-Smad2/3, increased cycling, and reduced long-term repopulating activity in HSCs. These results demonstrated for the first time that TGF-beta/Smad signaling is active in BM HSCs and maintains their dormancy. [Method: competitive repopulation assay, BM cells from Tgfbr2del/-Rag2-/- mice transplanted transplanted into B6-Ly5.2 mice, PB analysis after 16 weeks]
Formal Description Interaction-ID: 35290	gene/protein Tgfbr2 increases_activity of process repopulation >16 weeks in HSC (CD34-KSL) in vivo
Drugbank entries	Show/Hide entries for Tgfbr2
Drugbank DB04077	Glycerol not specified TGFBR2
Drugbank DB04077	Glycerol not specified TGFBR2

Comment	GFAP-positive glial cells (Schwann cells) express integrin-b8 in BM. [Method: glial cells, qRT-PCR]
Formal Description Interaction-ID: 35291	tissue/cell line non-myelinated Schwann cell (GFAP+) increases_expression of gene/protein Itgb8

Comment	Itgb8 activates Tgfbeta receptor, most likely by facilitating proteolytic degradation of LAP, which keeps the receptor in an inactive state, by matrix metalloproteinases. [Method: cited information]
Formal Description Interaction-ID: 35292	gene/protein Itgb8 increases_activity of complex/PPI Tgf-beta receptor

Comment	All GFAP-positive cells were positive for nestin and were positive for active Tgf-beta. [Method: immunohistochemistry]
Formal Description Interaction-ID: 35293	tissue/cell line non-myelinated Schwann cell (GFAP+) increases_quantity of gene/protein Nes

Comment	All GFAP-positive cells were positive for nestin and were positive for active Tgf-beta. [Method: immunohistochemistry]
Formal Description Interaction-ID: 35294	tissue/cell line non-myelinated Schwann cell (GFAP+) increases_activity of gene/protein Tgfbr2
Drugbank entries	Show/Hide entries for Tgfbr2
Drugbank DB04077	Glycerol not specified TGFBR2
Drugbank DB04077	Glycerol not specified TGFBR2

Comment	Itgb8 activates Tgfbeta receptor, most likely by facilitating proteolytic degradation of LAP, which keeps the receptor in an inactive state, by matrix metalloproteinases. [Method: cited information]
Formal Description Interaction-ID: 35295	gene/protein Itgb8 increases_activity of process transforming growth factor beta receptor signaling pathway

Comment	Loss of Tgfbr2 was associated with reduced p-Smad2/3, increased cycling, and reduced long-term repopulating activity in HSCs. These results demonstrated for the first time that TGF-beta/Smad signaling is active in BM HSCs and maintains their dormancy. [Method: BM section, FACS, fluorescence photomicrographs]
Formal Description Interaction-ID: 35296	process transforming growth factor beta receptor signaling pathway increases_activity of process SMAD protein signal transduction in HSC (CD34-KSL) in vivo

Comment	GFAP-expressing glial cells were in direct contact with about 23% of CD150+CD48-CD41-Lin- HSCs, whereas about 13% and 30% of HSCs were in contact, respectively, with osteocalcin-expressing osteoblastic cells and VE-cadherin expressing vascular cells. [Method: fluorescence micrographs]
Formal Description Interaction-ID: 35297	tissue/cell line non-myelinated Schwann cell (GFAP+) interacts (colocalizes) with Immunophenotype HSC (CD150+CD48-CD41-Lin-) about 23% of the HSCs were in contact with the Schwann cells in vivo

Comment	GFAP-expressing glial cells were in direct contact with about 23% of CD150+CD48-CD41-Lin- HSCs, whereas about 13% and 30% of HSCs were in contact, respectively, with osteocalcin-expressing osteoblastic cells and VE-cadherin expressing vascular cells. [Method: fluorescence micrographs]
Formal Description Interaction-ID: 35298	tissue/cell line osteoblast (osteocalcin+) interacts (colocalizes) with Immunophenotype HSC (CD150+CD48-CD41-Lin-) about 13% of the HSCs were in contact with osteocalcin-expressing osteoblasts in vivo

Comment	GFAP-expressing glial cells were in direct contact with about 23% of CD150+CD48-CD41-Lin- HSCs, whereas about 13% and 30% of HSCs were in contact, respectively, with osteocalcin-expressing osteoblastic cells and VE-cadherin expressing vascular cells. [Method: fluorescence micrographs]
Formal Description Interaction-ID: 35299	tissue/cell line sinusoidal endothelium (VE-cadherin+) interacts (colocalizes) with Immunophenotype HSC (CD150+CD48-CD41-Lin-) about 30% of the HSCs were in contact with VE-cadherin-expressing vascular cells in vivo

Comment	Schwann cells prepared from sciatic nerves expressed Tgfb1, Tgfb2, and Tgfb3 as well as Itgb8. Surprisingly, they also expressed major HSC niche factor genes, including Cxcl12, c-kit ligand (kitl), anginpoitin-1 (Angpt1), and Tpo. [Method: GFAP-positive primary glial cells were prepared from the sciatic nerve of adult C57BL/6 GFAP-GFP mice, qRT-PCR]
Formal Description Interaction-ID: 35300	tissue/cell line non-myelinated Schwann cell (GFAP+) increases_expression of gene/protein Tgfb1
Drugbank entries	Show/Hide entries for Tgfb1
Drugbank DB00070	Hyaluronidase inhibitor TGFB1

Comment	Schwann cells prepared from sciatic nerves expressed Tgfb1, Tgfb2, and Tgfb3 as well as Itgb8. Surprisingly, they also expressed major HSC niche factor genes, including Cxcl12, c-kit ligand (kitl), anginpoitin-1 (Angpt1), and Tpo. [Method: GFAP-positive primary glial cells were prepared from the sciatic nerve of adult C57BL/6 GFAP-GFP mice, qRT-PCR]
Formal Description Interaction-ID: 35301	tissue/cell line non-myelinated Schwann cell (GFAP+) increases_expression of gene/protein Tgfb2

Comment	Schwann cells prepared from sciatic nerves expressed Tgfb1, Tgfb2, and Tgfb3 as well as Itgb8. Surprisingly, they also expressed major HSC niche factor genes, including Cxcl12, c-kit ligand (kitl), anginpoitin-1 (Angpt1), and Tpo. [Method: GFAP-positive primary glial cells were prepared from the sciatic nerve of adult C57BL/6 GFAP-GFP mice, qRT-PCR]
Formal Description Interaction-ID: 35302	tissue/cell line non-myelinated Schwann cell (GFAP+) increases_expression of gene/protein Tgfb3
Drugbank entries	Show/Hide entries for Tgfb3
Drugbank DB03316	1,4-Diethylene Dioxide not specified TGFB3
Drugbank DB03316	1,4-Diethylene Dioxide not specified TGFB3

Comment	Schwann cells prepared from sciatic nerves expressed Tgfb1, Tgfb2, and Tgfb3 as well as Itgb8. Surprisingly, they also expressed major HSC niche factor genes, including Cxcl12, c-kit ligand (kitl), anginpoitin-1 (Angpt1), and Tpo. [Method: GFAP-positive primary glial cells were prepared from the sciatic nerve of adult C57BL/6 GFAP-GFP mice, qRT-PCR]
Formal Description Interaction-ID: 35303	tissue/cell line non-myelinated Schwann cell (GFAP+) increases_expression of gene/protein Itgb8

Comment	Schwann cells prepared from sciatic nerves expressed Tgfb1, Tgfb2, and Tgfb3 as well as Itgb8. Surprisingly, they also expressed major HSC niche factor genes, including Cxcl12, c-kit ligand (kitl), anginpoitin-1 (Angpt1), and Tpo. [Method: GFAP-positive primary glial cells were prepared from the sciatic nerve of adult C57BL/6 GFAP-GFP mice, qRT-PCR]
Formal Description Interaction-ID: 35304	tissue/cell line non-myelinated Schwann cell (GFAP+) increases_expression of gene/protein Cxcl12
Drugbank entries	Show/Hide entries for Cxcl12
Drugbank DB06822	Tinzaparin binder CXCL12

Comment	Schwann cells prepared from sciatic nerves expressed Tgfb1, Tgfb2, and Tgfb3 as well as Itgb8. Surprisingly, they also expressed major HSC niche factor genes, including Cxcl12, c-kit ligand (kitl), anginpoitin-1 (Angpt1), and Tpo. [Method: GFAP-positive primary glial cells were prepared from the sciatic nerve of adult C57BL/6 GFAP-GFP mice, qRT-PCR]
Formal Description Interaction-ID: 35305	tissue/cell line non-myelinated Schwann cell (GFAP+) increases_expression of gene/protein Kitl

Comment	Schwann cells prepared from sciatic nerves expressed Tgfb1, Tgfb2, and Tgfb3 as well as Itgb8. Surprisingly, they also expressed major HSC niche factor genes, including Cxcl12, c-kit ligand (kitl), anginpoitin-1 (Angpt1), and Tpo. [Method: GFAP-positive primary glial cells were prepared from the sciatic nerve of adult C57BL/6 GFAP-GFP mice, qRT-PCR]
Formal Description Interaction-ID: 35306	tissue/cell line non-myelinated Schwann cell (GFAP+) increases_expression of gene/protein Angpt1

Comment	Schwann cells prepared from sciatic nerves expressed Tgfb1, Tgfb2, and Tgfb3 as well as Itgb8. Surprisingly, they also expressed major HSC niche factor genes, including Cxcl12, c-kit ligand (kitl), anginpoitin-1 (Angpt1), and Tpo. [Method: GFAP-positive primary glial cells were prepared from the sciatic nerve of adult C57BL/6 GFAP-GFP mice, qRT-PCR]
Formal Description Interaction-ID: 35307	tissue/cell line non-myelinated Schwann cell (GFAP+) increases_expression of gene/protein Thpo

Comment	Loss of GFAP-positive cells results in loss of HSC (CD34-KSL). [Method: Glial cells deleted via Wallerian degeneration, frequency of CD34-KSL cells]
Formal Description Interaction-ID: 35308	tissue/cell line non-myelinated Schwann cell (GFAP+) increases_quantity of Immunophenotype HSC (CD34-KSL) in BM in vivo

Comment	Glial cells are responsible for the maintenance of HSC hibernation in BM by regulating the process by which latent TGF-beta is activated. [Method: CD34-KSL cells after denervation of sympathetic nerves, BrdU-labeling]
Formal Description Interaction-ID: 35309	tissue/cell line non-myelinated Schwann cell (GFAP+) increases_activity of process quiescence of HSC (CD34-KSL) in vivo

Comment	Glial cells are responsible for the maintenance of HSC hibernation in BM by regulating the process by which latent TGF-beta is activated. [Method: CD34-KSL cells after denervation of sympathetic nerves, BrdU-labeling]
Formal Description Interaction-ID: 35310	tissue/cell line non-myelinated Schwann cell (GFAP+) decreases_activity of process cell cycle in vivo

Comment	Activated Tgf-beta receptor RI/RII phosphorylates Smad2 and 3. In HSC (CD150+CD48-CD41-Lin-) Smad2 and 3 are phosphorylated. [Method: BM section, FACS, fluorescence photomicrographs]
Formal Description Interaction-ID: 35316	complex/PPI Tgf-beta receptor increases_activity of process SMAD protein signal transduction in HSC (CD150+CD48-CD41-Lin-)

Comment	All GFAP-positive cells were positive for nestin and were positive for active Tgf-beta. [Method: immunohistochemistry]
Formal Description Interaction-ID: 35318	tissue/cell line non-myelinated Schwann cell (GFAP+) increases_quantity of gene/protein Gfap

Comment	Smad2 and 3 are players of the SMAD signaling pathway. [Method: cited information]
Formal Description Interaction-ID: 35319	gene/protein Smad2 increases_activity of process SMAD protein signal transduction
Drugbank entries	Show/Hide entries for Smad2
Drugbank DB04522	Phosphonoserine not specified SMAD2
Drugbank DB04522	Phosphonoserine not specified SMAD2

Comment	Smad2 and 3 are players of the SMAD signaling pathway. [Method: cited information]
Formal Description Interaction-ID: 35320	gene/protein Smad3 increases_activity of process SMAD protein signal transduction

Comment	TGF-beta binds to its receptor composed of Tgf-betaRII and TGF-betaRI. [Method: cited information]
Formal Description Interaction-ID: 35321	gene/protein Tgfbr2 increases_activity of process transforming growth factor beta receptor signaling pathway
Drugbank entries	Show/Hide entries for Tgfbr2
Drugbank DB04077	Glycerol not specified TGFBR2
Drugbank DB04077	Glycerol not specified TGFBR2

Comment	TGF-beta binds to its receptor composed of Tgf-betaRII and TGF-betaRI. [Method: cited information]
Formal Description Interaction-ID: 36487	gene/protein Tgfbr1 increases_activity of process transforming growth factor beta receptor signaling pathway
Drugbank entries	Show/Hide entries for Tgfbr1
Drugbank DB03921	4-(3-Pyridin-2-Yl-1h-Pyrazol-4-Yl)Quinol ... not specified TGFBR1
Drugbank DB04434	Naphthyridine Inhibitor not specified TGFBR1
Drugbank DB04480	3-(4-Fluorophenyl)-2-(6-Methylpyridin-2- ... not specified TGFBR1
Drugbank DB07152	N-[4-(5-fluoro-6-methylpyridin-2-yl)-5-q ... not specified TGFBR1
Drugbank DB07267	2-(6-methylpyridin-2-yl)-N-pyridin-4-ylq ... not specified TGFBR1
Drugbank DB08450	N-1H-indazol-5-yl-2-(6-methylpyridin-2-y ... not specified TGFBR1

Comment	Itgb8 activates Tgfbeta receptor, most likely by facilitating proteolytic degradation of LAP, which keeps the receptor in an inactive state, by matrix metalloproteinases. [Method: immunohistochemistry]
Formal Description Interaction-ID: 37313	tissue/cell line non-myelinated Schwann cell (GFAP+) increases_activity of complex/PPI Tgf-beta receptor by expressing Itg8, the activator for latent TGF-beta

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