Activation of BNGR-A24 by direct interaction with tachykinin-related peptides from the silkworm Bombyx mori leads to the Gq- and Gs-coupled signaling cascades

Biochemistry. 2014 Oct 28;53(42):6667-78. doi: 10.1021/bi5007207. Epub 2014 Oct 16.

Abstract

Tachykinins constitute one of the largest peptide families in the animal kingdom and exert their diverse actions via G protein-coupled receptors (GPCRs). In this study, the Bombyx tachykinin-related peptides (TKRPs) were identified as specific endogenous ligands for the Bombyx neuropeptide GPCR A24 (BNGR-A24) and thus designated BNGR-A24 as BmTKRPR. Using both mammalian cell line HEK293 and insect cell line Sf21, further characterization demonstrated that BmTKRPR was activated, thus resulting in intracellular accumulation of cAMP, Ca(2+) mobilization, and ERK1/2 phosphorylation in a Gs and Gq inhibitor-sensitive manner. Moreover, quantitative reverse transcriptase polymerase chain reaction analysis and dsRNA-mediated knockdown experiments suggested a possible role for BmTKRPR in the regulation of feeding and growth. Our findings enhance the understanding of the Bombyx TKRP system in the regulation of fundamental physiological processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bombyx / metabolism*
  • Calcium / metabolism
  • Cloning, Molecular
  • Cyclic AMP / biosynthesis
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism*
  • GTP-Binding Protein alpha Subunits, Gs / metabolism*
  • HEK293 Cells
  • Humans
  • Ligands
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Neuropeptides / metabolism*
  • Phosphorylation
  • Receptors, Tachykinin / genetics
  • Receptors, Tachykinin / metabolism*
  • Sf9 Cells
  • Signal Transduction
  • Tachykinins / metabolism*

Substances

  • Ligands
  • Neuropeptides
  • Receptors, Tachykinin
  • Tachykinins
  • Cyclic AMP
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • GTP-Binding Protein alpha Subunits, Gs
  • Calcium