A phosphoproteomics approach to elucidate neuropeptide signal transduction controlling insect metamorphosis

Kim F. Rewitz, Martin R. Larsen, Anders Lobner-Olesen, Robert Rybczynski, Michael B. O'Connor, Lawrence I. Gilbert

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72 Scopus citations


In insects, the neuropeptide prothoracicotropic hormone (PTTH) stimulates production of ecdysone (E) in the prothoracic glands (PGs). E is the precursor of the principal steroid hormone, 20-hydroxyecdysone (20E), that is responsible for eliciting molting and metamorphosis. In this study, we used quantitative phosphoproteomics to investigate signal transduction events initiated by PTTH. We identified Spook (CYP307A1), a suspected rate-limiting enzyme for E biosynthesis, and components of the mitogen-activated protein kinase (MAPK) pathway, as major phosphorylation targets of PTTH signaling. Further, proteins not previously linked to PTTH and ecdysone biosynthesis were identified as targets of PTTH signaling. These include proteins involved in signal transduction, endosomal trafficking, constituents of the cytoskeleton and regulators of transcription and translation. Our screen shows that PTTH likely stimulates E production by activation of Spook, an integral enzyme in the E biosynthetic pathway. This directly connects PTTH signaling to the pathway that produces E. A new mechanism for regulation of E biosynthesis in insects is proposed.

Original languageEnglish (US)
Pages (from-to)475-483
Number of pages9
JournalInsect Biochemistry and Molecular Biology
Issue number7
StatePublished - Jul 2009

Bibliographical note

Funding Information:
We thank Peter Roepstorff for his views and ideas during the initial phase of the project, Lene Jakobsen for excellent technical support and Thomas Aarup Hansen for computational support for data analysis. We also thank James Warren for years of collaboration on the Halloween project. This work was supported by a fellowship (grant No. 272-07-0340) to K.F.R. from The Danish Natural Science Research Council and by grant IMB 0516623 to L.I.G from the National Science Foundation. M.R.L. was supported by The Danish Natural Science Research Council (grant No. 21-03-0167) and the Danish Strategic Research Council (Young Investigator award). M.B.O. is an investigator with the Howard Hughes Medical Institute.


  • 20-hydroxyecdysone
  • P450
  • PTTH
  • Phosphoproteomics
  • Spook
  • Titanium dioxide


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