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. 2020 Mar 3;11:100. doi: 10.3389/fendo.2020.00100

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Copyright © 2020 Duan and Allard.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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IGFBP-5 is part of a molecular switch that turns IGF signaling on or off in target cells. Zebrafish IGFBP-5a and the conserved zinc metalloproteinase Papp-aa are expressed in ionocytes. Left panel: under normal [Ca²⁺] conditions, Papp-a proteolysis activity is low. Igfbp5a is intact and it inhibits IGF signaling in these cells by binding to IGFs and prevents their binding to the IGF1R in ionocytes. Right panel: under low [Ca²⁺] conditions, Papp-a activity is increased. This increases IGFBP-5a proteolytic cleavage and releases IGFs from the IGFBP-5a/IGF complex to activate IGF-1 receptor-mediated PI3 kinase-Akt-Tor signaling and promotes ionocytes to proliferate.