Therapeutic targeting of insulin-regulated aminopeptidase: heads and tails?
Insulin-regulated aminopeptidase, IRAP, is an abundant protein that was initially cloned from a rat epididymal fat pad cDNA library as a marker protein for specialized vesicles containing the insulin-responsive glucose transporter GLUT4, wherein it is thought to participate in the tethering and trafficking of GLUT4 vesicles. The same protein was independently cloned from human placental cDNA library as oxytocinase and is proposed to have a primary role in the regulation of circulating oxytocin (OXY) during the later stages of pregnancy. More recently, IRAP was identified as the specific binding site for angiotensin IV, and we propose that it mediates the memory-enhancing effects of the peptide. This protein appears to have multiple physiological roles that are tissue- and domain-specific; thus the protein can be specifically targeted for treating different clinical conditions.
Albiston
Anthony L
AL
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria 3010, Australia.
Peck
Grantley R
GR
Yeatman
Holly R
HR
Fernando
Ruani
R
Ye
Siying
S
Chai
Siew Yeen
SY
D042964:Acyl-CoA Dehydrogenase / Q000378:metabolism; D000818:Animals; D003071:Cognition / Q000187:drug effects; D010122:Cystinyl Aminopeptidase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D020690:GTPase-Activating Proteins / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D008568:Memory / Q000187:drug effects; D051379:Mice; D036801:Parturition; D011480:Protease Inhibitors / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038501:Tankyrases / Q000378:metabolism
D042964:Acyl-CoA Dehydrogenase; D010122:Cystinyl Aminopeptidase; D020690:GTPase-Activating Proteins; D051275:Glucose Transporter Type 4; D011480:Protease Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D038501:Tankyrases; C518767:TBC1D4 protein, human; C418109:TNKS protein, human; C105964:leucyl-cystinyl aminopeptidase