Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.56 (insulin-degrading enzyme)
 737 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the binding and degradation of insulin-like growth factors (IGF)/somatomedin by rat kidney membrane using 125I-labeled IGF-I and IGF-II. The binding of IGF-I and IGF-II were specific to their respective kidney membrane receptors with indicated Mr of 130,000 and 250,000, respectively. The IGF-I and IGF-II degrading activities of the kidney membrane were also found to be specific for the respective hormones. Comparison of the binding and degrading kinetics suggested the two systems to be separate. The characterization of the degrading activities revealed the activities to be neutral sulfhydryl proteases which are different from insulin neutral protease. Identity of these proteases as separate from the insulin protease was revealed from the specificity of the degrading enzymes for IGF and the differential inhibitory effect of N-ethylmaleimide on the enzymes compared to insulin protease. In summary, the IGF binding and degrading activities of kidney membrane are two independent systems with specificity for IGF-I or IGF-II, respectively. Additionally, the characterized IGF-degrading systems revealed the enzymes to be different from the previously described insulin protease.
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PMID:Binding and degradation of insulin-like growth factors I and II by rat kidney membrane. 354 61

Physiologically, the action of insulin-like growth factors (IGFs) is controlled at different levels, from its transcription start by tissue-specific and development-specific transcriptional factors to its degradation by peptidases such as insulin-degrading enzyme (IDE). Since IGF-II is the major autocrine/paracrine growth factor for neuroblastoma cells, we studied the expression and the role of IDE in this system. Here, we show that (a) IDE is expressed in several human neuroectodermal tumor cell lines, including neuroblastoma cell lines; (b) in a neuroblastoma cell line, IDE expression is up-regulated by retinoic acid, a well-known inducer of neuronal differentiation and/or programmed cell death; (c) IDE is probably not the only IGF-degrading enzyme present in these cells, since the activity of a novel thermolysin-like metalloendopeptidase, clearly distinct from IDE, is also detected. The TME activity is inhibited by IGF-I, Des-IGF-I, and IGF-II, and it is down-regulated by retinoic acid. Since retinoic acid plays a relevant role in controlling the growth of these cells and affects the expression of IDE, we have also: (a) identified the retinoic acid receptors (RARs) and retinoid X receptors (RXRs) expressed in these cell lines and (b) by means of synthetic retinoid analogues identified the RAR/RXR isoforms whose activation may be sufficient to induce the expression of the IDE gene. These results provide evidence that complex posttranslational molecular mechanisms participate in the autocrine/paracrine growth control of the IGF-II loop in neuroblastomas involving proteolytic systems.
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PMID:Regulation by retinoic acid of insulin-degrading enzyme and of a related endoprotease in human neuroblastoma cell lines. 878 Aug 92