TY - GEN
T1 - Degradation of relaxin family peptides by insulin-degrading enzyme
AU - Bennett, Robert G.
AU - Heimann, Dean G.
AU - Hamel, Frederick G.
PY - 2009/4
Y1 - 2009/4
N2 - Insulin-degrading enzyme (IDE) is a ubiquitously expressed metalloproteinase responsible for the intracellular degradation of insulin. IDE also interacts with other members of the insulin superfamily, including relaxin, but no studies have been reported regarding the interaction of other relaxin-like peptides with IDE. In this study, we determined that relaxin, relaxin-3, and InsL3 all competitively inhibited the degradation of insulin by IDE to different degrees, and all inhibited covalent cross-linking of insulin to IDE. Each of the peptides was degraded by IDE to various degrees (insulin > relaxin > InsL3 = relaxin-3). In summary, relaxin, InsL3, and relaxin-3 all bound to IDE, competed for the binding and degradation of insulin, and were all substrates for the proteolytic activity of IDE. Therefore, it is possible that in addition to insulin, IDE may be important for the cellular proteolysis of relaxin, InsL3, and relaxin-3.
AB - Insulin-degrading enzyme (IDE) is a ubiquitously expressed metalloproteinase responsible for the intracellular degradation of insulin. IDE also interacts with other members of the insulin superfamily, including relaxin, but no studies have been reported regarding the interaction of other relaxin-like peptides with IDE. In this study, we determined that relaxin, relaxin-3, and InsL3 all competitively inhibited the degradation of insulin by IDE to different degrees, and all inhibited covalent cross-linking of insulin to IDE. Each of the peptides was degraded by IDE to various degrees (insulin > relaxin > InsL3 = relaxin-3). In summary, relaxin, InsL3, and relaxin-3 all bound to IDE, competed for the binding and degradation of insulin, and were all substrates for the proteolytic activity of IDE. Therefore, it is possible that in addition to insulin, IDE may be important for the cellular proteolysis of relaxin, InsL3, and relaxin-3.
KW - InsL3
KW - Insulin-degrading enzyme
KW - Insulysin
KW - Relaxin
KW - Relaxin-3
KW - Relaxin-like factor
UR - http://www.scopus.com/inward/record.url?scp=64549147968&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=64549147968&partnerID=8YFLogxK
U2 - 10.1111/j.1749-6632.2008.03782.x
DO - 10.1111/j.1749-6632.2008.03782.x
M3 - Conference contribution
C2 - 19416156
AN - SCOPUS:64549147968
SN - 9781573317214
T3 - Annals of the New York Academy of Sciences
SP - 38
EP - 41
BT - Relaxin and Related Peptides Fifth International Conference
PB - Blackwell Publishing Inc.
ER -