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 -