Drosophila Smad2 degradation occurs independently of linker phosphorylations
Abstract
TGF-β signals are important for proliferation, differentiation, and cell fate determination during embryonic development and tissue homeostasis in adults. Drosophila Activin/TGF-β signals are transduced intracellularly when its transcription factor dSmad2 (also called Smad on X or Smox) is C-terminally phosphorylated by pathway receptors. Recently, it has been shown that receptor-activated dSmad2 undergoes bulk degradation, however, the mechanism of how this occurs is unknown. Here we investigated if two putative linker phosphorylation sites are involved in dSmad2 degradation. We demonstrate that degradation of activated-dSmad2 occurs independently of threonine phosphorylation at linker sites 252 and 277. We also show that dSmad2 degradation is not carried out by cellular proteasomes.
Copyright and License
© 2024 by the authors. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Acknowledgement
We thank the Developmental Studies Hybridoma Bank for the Tubulin and Armadillo antibodies. We thank Michael O' Connor for the Activated Baboon construct.
Funding
Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institute of Health under Award Number R25GM061331 (K.C. and P.F.), T34GM145503 (JG), and R15GM123374 (E.E.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health. N.P. was supported by the National Science Foundation under grant HRD-1700556; H.U. was supported by the National Science Foundation under grant HRD-1602210.
Contributions
- Kenny Castro: Investigation, Methodology, Writing - review & editing, Data curation
- Volodia Muradyan: Data curation, Investigation, Writing - review & editing
- Pablo Flota: Data curation, Investigation, Writing - review & editing
- John Guanzon: Data curation, Writing - review & editing
- Neil Poole: Data curation, Investigation
- Hugo Urrutia: Conceptualization, Investigation, Data curation, Writing - review & editing
- Edward Eivers: Conceptualization, Formal analysis, Funding acquisition, Project administration, Supervision, Writing - original draft, Writing - review & editing, Investigation
Files
micropub-biology-001153.pdf
Additional details
Identifiers
- PMCID
- PMC11004797
Funding
- National Institutes of Health
- R25GM061331
- National Institutes of Health
- NIH Predoctoral Fellowship T34GM145503
- National Institutes of Health
- R15GM123374
- National Science Foundation
- EES-1700556
- National Science Foundation
- EES-1602210