A phosphoproteomics approach to elucidate neuropeptide signal transduction controlling insect metamorphosis

TY - JOUR

T1 - A phosphoproteomics approach to elucidate neuropeptide signal transduction controlling insect metamorphosis

AU - Rewitz, Kim F

AU - Larsen, Martin R

AU - Lobner-Olesen, Anders

AU - Rybczynski, Robert

AU - O'Connor, Michael B

AU - Gilbert, Lawrence I

PY - 2009/7

Y1 - 2009/7

N2 - 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.

AB - 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.

KW - Amino Acid Sequence

KW - Animals

KW - Ecdysone/biosynthesis

KW - Insect Hormones/genetics

KW - Insect Proteins/chemistry

KW - Manduca/chemistry

KW - Metamorphosis, Biological

KW - Mitogen-Activated Protein Kinases/genetics

KW - Molecular Sequence Data

KW - Molting

KW - Phosphoproteins/chemistry

KW - Phosphorylation

KW - Proteomics/methods

KW - Sequence Alignment

KW - Signal Transduction

U2 - 10.1016/j.ibmb.2009.04.005

DO - 10.1016/j.ibmb.2009.04.005

M3 - Journal article

C2 - 19422916

SN - 0965-1748

VL - 39

SP - 475

EP - 483

JO - Insect Biochemistry and Molecular Biology

JF - Insect Biochemistry and Molecular Biology

IS - 7

ER -