Angiopoietin 1 (Ang-1 proteins and Antibodies)

 Angiopoietin 2 (Ang-2 proteins and Antibodies)
 

Angiopoietin 3-4(Ang-3 and Ang-4 proteins and Antibodies)
 

M= Mouse; R=Rat; H=Human; Rb=Rabbit; G=goat; B=Bovine, MO=Monkey; P=pig; CT= near C-terminus; NT=near N-terminus; Internal=Middle of protein. EC=extracellular; CP=cytoplasmic domains *

Related Items TIEs (Tek), VEGF, and VEGF Receptors 1-3 (FLK-1, Flt-1, and Flt-4) Antibodies

Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) General Information

Embryonic vascular system undergoes a series of complex, highly regulated series of events involving differentiation, migration and association of primitive endothelial cells. This process is termed vasculogenesis. A further remodeling of the primitive vascular system forms the mature cardiovascular system. This process is known as angiogenesis (sprouting of new capillary vessels from pre-existing vasculature). The development of primordia of the heart and large vessels, primary capillary networks in the embryo and the extraembryonic structures in the yolk sac. Angiogenesis accounts for the formation of vasculature into previously avascular organs such as brain and kidney. Angiogenic activity in the adult is required during the normal tissue repair, and for the remodeling of the female reproductive organs (ovulation and placental development). Certain pathological conditions, such as tumor growth and diabetic retinopathy, also require angiogenesis. The genetic and molecular mechanism that influence angiogenesis has only recently begun to be studied and identified. Study of tumor angiogenesis has led to the identification of several proteins including basic fibroblast growth factor (bFGF) and vascular endothelial growth factor. VEGF acts by interacting with a family of largely endothelial-specific receptor tyrosine kinases that includes VEGFR-1 (flt-1), VEGFR-2 (flk-1/KDR), and VEGFR-3/Flt-4. Disruption of VEGFRs interferes with differentiation of endothelial cells and it is lethal for the embryo.

Angiopoietin-1 (mouse and human Ang-1; 498 AA; ~ 98% identity) is an angiogenic secreted protein that interact with endothelial specific Tie-2 receptor. During embryonic development, Ang-1 binds and induces tyrosine phosphorylation of Tie-2. Ang-1 deficient mice mimic the phenotype exhibited by animals deficient in Tie-2. The role of Ang-1 in angiogenesis appears to be different from VEGF. A homolog of Ang-1, termed Angiopoietin-2 (mouse and human Ang-2, 496 AA; ~85% identity) has recently been identified. It may act an antagonist for Ang-1 and Tie-2. Ang-1 and Ang-2 have ~60% sequence homology.

Ang-1 is prominently expressed in the myocardium of atrium and ventricle, mesenchymal and smooth muscle cells surrounding most blood vessels, and lung. Ang-2 expression is abundant in the dorsal aorta and major aortic branches. Ang-2 transcripts in fetal liver were restricted to cells at the lumen of hepatic vessels. In the adult, Ang-1 was also expressed in the heart and liver. In contrast, Ang-2 was found in tissues that may undergo vascular remodeling (ovary, placenta, and uterus). Defects in Tie-2 have been linked to dominantly negative venous malformation, an error of vascular morphogenesis characterized by dilated serpiginous channels.

A homology-based cloning approach has led to the identification of angiopoietin-3 (Angpt3, 509 aa, chromosome 2) in mouse, and angiopoietin-4 (ANGPT4, 504 aa, chromosome 20p13) in human. Although angiopoietin-3 and angiopoietin-4 are more structurally diverged from each other than are the mouse and human versions of angiopoietin-1 and angiopoietin-2, they appear to represent the mouse and human counterparts of the same gene locus, as revealed in chromosomal localization studies of all the angiopoietins in mouse and human. Angiopoietin-3 was expressed as multiple mouse tissues , whereas angiopoietin-4 was expressed primarily in human lung. It is also suggested that angiopoietin-3 acts as an antagonist, whereas angiopoietin-4 functions as an agonist.