Angiopoietins 3 and 4: diverging gene counterparts in mice and humans.
The angiopoietins have recently joined the members of the vascular endothelial growth factor family as the only known growth factors largely specific for vascular endothelium. The angiopoietins include a naturally occurring agonist, angiopoietin-1, as well as a naturally occurring antagonist, angiopoietin-2, both of which act by means of the Tie2 receptor. We now report our attempts to use homology-based cloning approaches to identify new members of the angiopoietin family. These efforts have led to the identification of two new angiopoietins, angiopoietin-3 in mouse and angiopoietin-4 in human; we have also identified several more distantly related sequences that do not seem to be true angiopoietins, in that they do not bind to the Tie receptors. Although angiopoietin-3 and angiopoietin-4 are strikingly 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 our chromosomal localization studies of all of the angiopoietins in mouse and human. The structural divergence of angiopoietin-3 and angiopoietin-4 appears to underlie diverging functions of these counterparts. Angiopoietin-3 and angiopoietin-4 have very different distributions in their respective species, and angiopoietin-3 appears to act as an antagonist, whereas angiopoietin-4 appears to function as an agonist.
Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA.
D M
DM
Valenzuela
J A
JA
Griffiths
J
J
Rojas
T H
TH
Aldrich
P F
PF
Jones
H
H
Zhou
J
J
McClain
N G
NG
Copeland
D J
DJ
Gilbert
N A
NA
Jenkins
T
T
Huang
N
N
Papadopoulos
P C
PC
Maisonpierre
S
S
Davis
G D
GD
Yancopoulos
D000595:Amino Acid Sequence; D042683:Angiopoietin-1; D000091304:Angiopoietin-Like Protein 1; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D000818:Animals; D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20; D002898:Chromosomes, Human, Pair 8; D019143:Evolution, Molecular; D005260:Female; D014644:Genetic Variation; D006133:Growth Substances / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011247:Pregnancy; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D042787:Receptor, TIE-2; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
C467630:ANGPT1 protein, human; C117578:ANGPTL1 protein, human; D042683:Angiopoietin-1; D000091304:Angiopoietin-Like Protein 1; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C467628:Angpt1 protein, mouse; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D011506:Proteins; C118117:angiopoietin 4; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2