Phospholipase C Gamma 1 Connects the Cell Membrane Pathway to the Nuclear Receptor Pathway in Insect Steroid Hormone Signaling [Cell Biology]

April 1st, 2014 by Liu, W., Cai, M.-J., Zheng, C.-C., Wang, J.-X., Zhao, X.-F.

In addition to the classical nuclear receptor pathway, there is a non-genomic pathway in the cell membrane that regulates gene expression in animal steroid hormone signaling; however, this mechanism is unclear. Here, we report that the insect steroid hormone 20-hydroxyecdysone (20E) regulates calcium influx via phospholipase C gamma 1 (PLCG1) to modulate the protein kinase C (PKC) phosphorylation of the transcription factor ultraspiracle (USP1) in the lepidopteran insect Helicoverpa armigera. The PLCG1 mRNA levels are increased during the molting and metamorphic stages. The depletion of PLCG1 by RNA interference can block 20E-enhanced pupation, cause larvae death and pupation defects, and repress 20E-induced gene expression. 20E may induce the tyrosine phosphorylation of PLCG1 at the cytosolic tyrosine kinase (Src) homology (SH) 2 domains, and then determine the migration of PLCG1 toward the plasma membrane. The G-protein-coupled-receptor (GPCR) inhibitor suramin, Src-family kinases inhibitor PP2, and the depletions of ecdysone-responsible GPCR (ErGPCR) and G-protein alpha q (Gαq) restrain the 20E-induced tyrosine phosphorylation of PLCG1. PLCG1 participates in the 20E-induced Ca2+ influx. The inhibition of GPCR, PLC, inositol 1,4,5-trisphosphate receptor, and calcium channels represses the 20E-induced Ca2+ influx. Through calcium signaling, PLCG1 mediates the transcriptional activation driven by the ecdysone response element (EcRE). Through PLCG1 and calcium signaling, 20E regulates PKC phosphorylation of USP1 at Ser21 to determine its EcRE binding activity. These results suggest that 20E activates PLCG1 via ErGPCR and Src-family kinases to regulate Ca2+ influx and PKC phosphorylation of USP1 in order to subsequently modulate gene transcription.
  • Posted in Journal of Biological Chemistry, Publications
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