CDB15:0000054 ANGPT1 — ITGB1

Experimentally validated in Human, Mixed species, Mouse, Rat; Orthology-inferred in Human, Mouse, Frog, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep, Rat

Title

Journal:; Year Published:

Abstract

Vascular-specific growth factor angiopoietin 1 is involved in the organization of neuronal processes.

The Journal of comparative neurology, 2005; PubMed, Homo sapiens ANGPT1 — Mus Musculus Itgb1
ABSTRACT: Neuronal processes and vessels have similar branching and bifurcation patterning in the adult body and appear to use many of the same molecules during their development, including vascular endothelial growth factor, Notch, neuropilin, and ephrins/Ephs. We were interested in determining whether the endothelial growth factor angiopoietin (Ang) has a unique role in the nervous system in addition to its angiogenic role. By using a mouse molecular genetics approach, we overexpressed Ang1 in the mouse forebrain and observed increases in overall vascularization, consistent with prior reports describing the role of Ang1. Nonvascular events, involving alterations in the dendritic organization of layer II motor cortex neurons, dentate granule cells, and pyramidal cells of CA1, were seen, suggesting that Ang1 was able to influence the growth of these processes. The angiopoietin tyrosine kinase receptor Tie2 was not found on neurons or their processes, but beta1 integrin was and has previously been found to act as an Ang receptor. Our findings provide some of the first data evaluating the interactions between the developing nervous system and the vascular protein Ang1. Understanding interactions between the developing nervous and vascular systems will lead to novel insight into how the two systems interact throughout development, during senescence, and in disease.

Effects of protein and gene transfer of the angiopoietin-1 fibrinogen-like receptor-binding domain on endothelial and vessel organization.

The Journal of biological chemistry, 2005; PubMed, Homo sapiens ANGPT1 — Homo sapiens ITGB1
ABSTRACT: The vessel-stabilizing effect of angiopoietin-1 (Ang1)/Tie2 receptor signaling is a potential target for pro-angiogenic therapies as well as anti-angiogenic inhibition of tumor growth. We explored the endothelial and vascular specific activities of the Ang1 monomer, i.e. dissociated from its state as an oligomer. A truncated monomeric Ang1 variant (i.e. DeltaAng1) containing the isolated fibrinogen-like receptor-binding domain of Ang1 was created and recombinantly produced in insect cells. DeltaAng1 ligated the Tie2 receptor without triggering its phosphorylation. Moreover, monomeric DeltaAng1 was observed to bind alpha(5)beta(1) integrin with similar affinity compared with Tie2. Unexpectedly, in vitro treatment of endothelial cells with DeltaAng1 showed some of the known effects of full-length Ang1, including inhibition of basal endothelial cell permeability and stimulation of cell adhesion as well as activation of MAPKs. Local treatment of the microvasculature of the developing chicken chorioallantoic membrane with the DeltaAng1 protein led to profound reduction of the mean vascular length density, thinning of vessels, and reduction of the number of vessel branching points. Similar effects were observed in side-by-side experiments with the recombinant full-length Ang1 protein. These effects of simplification of the vessel branching pattern were confirmed through local gene transfer with lentiviral particles encoding DeltaAng1 or full-length Ang1. Together, our findings suggest a potential use for exogenous Ang1 in reducing rather than increasing vascular density. Furthermore, we show that the isolated receptor-binding domain of Ang1 is capable of mediating some effects of full-length Ang1 independently of Tie2 phosphorylation, possibly through integrin ligation.

Angiopoietin-1 induces neurite outgrowth of PC12 cells in a Tie2-independent, beta1-integrin-dependent manner.

Neuroscience research, 2009; PubMed, Mus Musculus Angpt1 — Rattus norvegicus Itgb1
ABSTRACT: Overexpression of angiopoietin (Ang) 1 in the brain results in increased vascularization and altered neuronal dendrite configuration. We hypothesized that Ang1 acts directly on neurons inducing neurite outgrowth. We stimulated PC12 cells with Ang1 and observed outgrowth levels comparable to nerve growth factor (NGF). Western blotting and RT-PCR demonstrated the absence of the Ang1 receptor, Tie2 and the presence of beta1-integrin. Downstream of beta1-integrin, Ang1 stimulation led to a approximately 2.6 fold increase in focal adhesion kinase (FAK) phosphorylation and no change in the activation of mitogen-activated protein kinase (MAPK) nor c-Jun N-terminal kinase (JNK). Conversely, NGF stimulation had no effect on FAK phosphorylation but led to a approximately 3.1 and approximately 2 fold increase in phosphorylation of MAPK and JNK. Ang1, but not NGF-mediated outgrowth was attenuated following functional inhibition of beta1-integrin and FAK, and Wortmannin inhibited neurite outgrowth mediated by both. Our results suggest that Ang1 induces neurite outgrowth in PC12 cells in a Tie2-independent, beta1-integrin-FAK-PI3K-Akt-dependent manner and that NGF and Ang1 mediate neurite outgrowth via two independent signaling mechanisms.
Basic Information on ANGPT1
Ligand Name: angiopoietin 1
Other Symbols: KIAA0003, Ang1, AGPT-1
Ligand Location: secreted based on perplexity, uniprot
HGNC Gene Symbol Report: ANGPT1
GeneCards: ANGPT1
Interactions with other Receptors for ANGPT1
Basic Information on ITGB1
Receptor Name: integrin subunit beta 1
Other Symbols: FNRB, MSK12, MDF2, CD29, GPIIA
Receptor Location: cell membrane based on hpa, perplexity, uniprot
HGNC Gene Symbol Report: ITGB1
GeneCards: ITGB1
HGNC Gene Group: CD molecules, Integrins
Interactions with other Ligands for ITGB1
ADAM12 — ITGB1ADAM15 — ITGB1ADAM17 — ITGB1ADAM2 — ITGB1ADAM9 — ITGB1CD14 — ITGB1CHAD — ITGB1COL11A1 — ITGB1COL18A1 — ITGB1COL1A1 — ITGB1COL1A2 — ITGB1COL2A1 — ITGB1COL3A1 — ITGB1COL4A1 — ITGB1COL4A3 — ITGB1COL4A4 — ITGB1COL4A5 — ITGB1COL4A6 — ITGB1COL5A1 — ITGB1CXCL12 — ITGB1F13A1 — ITGB1FBLN1 — ITGB1FBN1 — ITGB1FGA — ITGB1VEGFD — ITGB1FN1 — ITGB1HSPG2 — ITGB1ICAM4 — ITGB1LAMA1 — ITGB1LAMA2 — ITGB1LAMA4 — ITGB1LAMA5 — ITGB1LAMB1 — ITGB1LAMB3 — ITGB1LAMC1 — ITGB1LAMC2 — ITGB1LGALS3BP — ITGB1MATN1 — ITGB1MDK — ITGB1NID1 — ITGB1NPNT — ITGB1PLG — ITGB1RELN — ITGB1SEMA7A — ITGB1SPP1 — ITGB1TGM2 — ITGB1THBS1 — ITGB1THBS2 — ITGB1TIMP2 — ITGB1TNC — ITGB1VCAM1 — ITGB1VCAN — ITGB1VEGFA — ITGB1VEGFC — ITGB1VTN — ITGB1ANGPTL2 — ITGB1CCN4 — ITGB1CLEC11A — ITGB1LGALS1 — ITGB1PLA2G2A — ITGB1SPON2 — ITGB1ADAM28 — ITGB1AGGF1 — ITGB1AGRN — ITGB1ANGPT2 — ITGB1ANGPTL4 — ITGB1CCN2 — ITGB1CCN3 — ITGB1CD40LG — ITGB1CDH1 — ITGB1COL10A1 — ITGB1COL11A2 — ITGB1COL13A1 — ITGB1COL4A2 — ITGB1COL8A1 — ITGB1COL8A2 — ITGB1CSPG4 — ITGB1CX3CL1 — ITGB1ICAM5 — ITGB1IL1B — ITGB1JAM2 — ITGB1L1CAM — ITGB1LAMA3 — ITGB1LAMB2 — ITGB1LGALS3 — ITGB1LGALS8 — ITGB1MFGE8 — ITGB1MIA — ITGB1NTN4 — ITGB1PLAUR — ITGB1SVEP1 — ITGB1TGFB1 — ITGB1TGFB3 — ITGB1THBS4 — ITGB1THY1 — ITGB1TIMP1 — ITGB1VWF — ITGB1