DEFINITION
Angiopoietins are proteins with important roles in vascular development and angiogenesis.
All angiopoietins bind with similar affinity to an endothelial cell-specific tyrosine-protein kinase receptor.
The protein encoded by this gene is a secreted glycoprotein that activates the receptor by inducing its tyrosine phosphorylation.
It plays a critical role in mediating reciprocal interactions between the endothelium and surrounding matrix and mesenchyme. The protein also contributes to blood vessel maturation and stability, and may be involved in early development of the heart.There are now four identified angiopoietins: Ang1, Ang2, Ang3, Ang4. Angiopoietin 1 is a type of angiopoietin and is encoded by the gene ANGPT1. Wikipedia
Immunofluorescence - Angiopoietin 1
Angiopoietin 1 antibody
CHEMICAL STRUCTURE AND IMAGES
Primary structure:
uniprot
Secondary structure
Oligomerization and Multimerization Are Critical for Angiopoietin-1 to Bind and Phosphorylate Tie2,2005
Tertiary structure
Protein Aminoacids Percentage
SYNTHESIS AND TURNOVER
mRNA synthesis
Two principal angiopoietin isoforms have been identified, angiopoietin-1 (Ang-1), which activates TIE-2 and angiopoietin-2 (Ang-2), a putative endogenous TIE-2 receptor antagonist, thought to be a competitive inhibitor of the actions of Ang-1. Ang-1 and TIE-2 appear to be widely expressed in the quiescent vasculature, whereas Ang-2 is expressed only at sites of vascular remodeling. Myocardial ischemia induced by left coronary artery ligation resulted: at 24 h, Ang-1 mRNA and protein expression within the infarct and peri-infarct regions were decreased compared to non-infarcted myocardium, whereas Ang-2 mRNA levels were markedly increased and TIE-2 expression was unchanged. At 1 week, Ang-1 expression was partially restored, whereas Ang-2 expression remained elevated. At the time of peak elevation in Ang-2, Tie2 phosphorylation was found to be markedly increased, consistent with receptor activation.
Reciprocal regulation of angiopoietin-1 and angiopoietin-2 following myocardial infarction in the rat,2004
protein synthesis
The Ang1 structure consists of a carboxyl-terminal fibrinogen-like domain that is responsible for receptor binding, a central coiled-coil domain that may be responsible for oligomerizing these fibrinogen-like domains, and a short amino-terminal domain that superclusters these oligomers into variably sized multimers. To achieve Tie2 receptor oligomerization and activation, Ang1 uses an oligomeric and multimeric structure unlike that of any other known growth factor. Ang1 exists as heterogeneous multimers with basic trimeric, tetrameric, and pentameric oligomers. proper oligomerization of Ang1 having at least four subunits by the intermolecular disulfide linkage involving cysteines 41 and 54 is critical for Tie2 binding and activation.
Oligomerization and Multimerization Are Critical for Angiopoietin-1 to Bind and Phosphorylate Tie2,2005
CELLULAR FUNCTIONS
Cellular localization:
Ang-1 administered in vivo is mainly localized to microvascular endothelial cells of the intestinal villi and lung but not to microvascular endothelial cells of the liver.
BIOLOGICAL FUNCTION
Angiopoietins are vascular endothelial cell-specific growth factors that play important roles principally during the later stages of angiogenesis, after the induction of new capillaries by vascular endothelial growth factor (VEGF). Our results indicate that Angiopoietin-1 is indeed a primary physiologic ligand for TIE2; that it has critical in vivo actions during angiogenesis that appear to occur later than those of VEGF; and that these in vivo actions are not reflected in the classic in vitro assays.
Requisite Role of Angiopoietin-1, a Ligand for the TIE2 Receptor, during Embryonic Angiogenesis,1996
There are four known angiopoietins, and their specificity for the vascular endothelium results from the restricted expression pattern of their tyrosine kinase receptor, Tie2. Ang-1/ Tie-2 signaling promotes angiogenesis during the development, remodeling, and repair of the vascular system.
Postnatally, the angiogenic activity of Ang-1/Tie-2 is required during normal tissue repair and remodeling of the female endometrium in the menstrual cycle. In addition to suppressing endothelial cell activation by inhibiting the expression of adhesion and inflammatory molecules, Ang-1 enhances endothelial cell survival and capillary morphogenesis, and lessens capillary permeability.
Recombinant Proteins ANG-1 Recombinant Protein
Paradox of opposing activities of ang-1 and ang-2. Both ang-1 and ang-2 act at the tie-2 receptor, and stimulate phosphoinositol 3 kinase/akt signaling. However, ang-1 stabilizes endothelium and inhibits vascular permeability, whereas ang-2 destabilizes endothelium and increases vascular permeability. Ang-2 may act by not only stimulating phosphoinositol 3 kinase/akt, but also by inducing reactive oxygen. This may occur at the level of crosstalk or even heterodimerization.
The Duality of Angiogenesis: Implications for Therapy of Human Disease,2006
REGULATION
Tie-2 gene expression is upregulated in low oxygen tensions through hypoxia-inducible factor–induced transcriptional activation. Ang-1/Tie-2 signaling appears to be regulated by Angiopoietin-2 (Ang-2), a natural antagonist for Tie-2 that exerts its effects through an internal autocrine loop mechanism. Ang1 induces trans-association of Tie2 at cell-cell contacts, whereas Tie2 is anchored to the extracellular matrix (ECM) by Ang1 at the cell-substratum interface.
Angiopoietin-1/Tie2 receptor signaling in vascular quiescence and angiogenesis,2010
Ang-1 promotes EC chemotaxis through tie-2 receptor activation. The chemotactic effects of Ang-1 on cultured ECs was significantly attenuated in cells overexpressing SOD, catalase, Rac1N17. NADPH oxidase-derived ROS play an important role in promoting the chemotactic effects of Ang-1.
Roles of reactive oxygen species in angiopoietin-1/tie-2 receptor signaling,2005
DIAGNOSTIC USE
The increase/decrease in angiopoietin 1 in serum may be indicative of different diseases:
Angiopoiein-1 expression is enhanced in Behçet's disease (BD) patients compared to controls. Serum angiopoietin-1 expression is significantly elevated in patients with skin lesions and positively correlated with disease duration.
Serum angiopoietin-1 level is increased in patients with Behçet's disease,2010
Angiopoietin-1 levels were significantly lower in inflammatory bowel disease (IBD) patients compared to controls and increased in smokers compared to nonsmoker ulcerative colitis (UC) patients.
Angiogenin, angiopoietin-1, angiopoietin-2, and endostatin serum levels in inflammatory bowel disease,2011
In patients with acute myocardial infarction (MI) Ang-1 levels were unchanged from baseline (on admission) to 6 weeks but were elevated at 18 weeks. Serial changes in the plasma levels may reflect the progressive stages of angiogenesis activity in the ischemic-necrotic myocardium in vivo.
Plasma Angiopoietin-1, Angiopoietin-2, Angiopoietin Receptor Tie-2, and Vascular Endothelial Growth Factor Levels in Acute Coronary Syndromes,2004
