Binding requirements for latent transforming growth factor Beta2 activation.
| Autor: | Sachan N; Department of Cell Biology, NYU Grossman School of Medicine, New York, NY 10016, USA., Phoon CKL; Department of Pediatrics, NYU Grossman School of Medicine, New York, NY 10016, USA., Bu L; Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA., Zilberberg L; Department of Cell Biology, NYU Grossman School of Medicine, New York, NY 10016, USA., Ahamed J; Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA., Rifkin DB; Department of Cell Biology, NYU Grossman School of Medicine, New York, NY 10016, USA.; Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA. |
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| Jazyk: | angličtina |
| Zdroj: | Matrix biology plus [Matrix Biol Plus] 2024 May 14; Vol. 22, pp. 100149. Date of Electronic Publication: 2024 May 14 (Print Publication: 2024). |
| DOI: | 10.1016/j.mbplus.2024.100149 |
| Abstrakt: | Although the mechanism for activation of latent TGFβ1 and TGFβ3 is understood to involve the binding of the TGFβ propeptide (LAP) to both an integrin and an insoluble substrate, the activation of latent TGFβ2 has been unclear because the TGFβ2 LAP does not have the classical integrin binding sequence found in the other two TGFβ isoform LAPs. To assess the potential requirement for covalent linkage with a matrix or cell surface protein for the activation of latent TGFβ2, we generated mice in which the TGFβ2 Cys residue predicted to be involved in binding was mutated to Ser ( Tgfb2 C24S ). We reasoned that, if covalent interaction with a second molecule is required for latent TGFβ2 activation, mutant mice should display a Tgfb2 null ( Tgfb2 -/- )-like phenotype. Tgfb2 C24S mice closely phenocopy Tgfb2 -/- mice with death in utero between E18 and P1 and with congenital heart and kidney defects similar to those described for Tgfb2 -/- mice. The mutant latent TGFβ2 is secreted at levels similar to WT, yet TGFβ signaling monitored as nuclear pSmad2 is suppressed. We conclude that, like latent TGFβ1, latent TGFβ2 activation requires binding to an immobilized matrix or plasma membrane molecule. Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Daniel B Rifkin reports financial support was provided by National Heart Lung and Blood Institute. Jasimuddin Ahamed reports financial support was provided by National Heart Lung and Blood Institute. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 Published by Elsevier B.V.) |
| Databáze: | MEDLINE |
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