title: The Steroid Hormone 20-Hydroxyecdysone Enhances Gene Transcription through the cAMP Response Element-binding Protein (CREB) Signaling Pathway.
abstract: Animal steroid hormones regulate gene transcription through genomic pathways by binding to nuclear receptors. These steroid hormones also rapidly increase intracellular calcium and cyclic adenosine monophosphate (cAMP) levels and activate the protein kinase C (PKC) and protein kinase A (PKA) nongenomic pathways. However, the function and mechanism of the nongenomic pathways of the steroid hormones are unclear, and the relationship between the PKC and PKA pathways is also unclear. We propose that the steroid hormone 20-hydroxyecdysone (20E) activates the PKA pathway to enhance 20E-induced gene transcription in the lepidopteran insect Helicoverpa armigera The expression of the catalytic subunit 1 of PKA (PKAC1) increased during metamorphosis, and PKAC1 knockdown blocked pupation and repressed 20E-responsive gene expression. 20E regulated PKAC1 phosphorylation at threonine 200 and nuclear translocation through an ecdysone-responsive G-protein-coupled receptor 2. PKAC1 induced cAMP response element-binding protein (CREB) phosphorylation at serine 143, which bound to the cAMP response element on DNA to enhance 20E-responsive gene transcription. Through ecdysone-responsive G-protein-coupled receptor 2, 20E increased cAMP levels, which induced CREB PKA phosphorylation and 20E-responsive gene expression. This study demonstrates that the PKA/CREB pathway tightly and critically regulates 20E-induced gene transcription as well as its relationship with the 20E-induced PKC pathway.
authors.affiliation: From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan 250100, China.
authors.forename: Yu-Pu
authors.initials: YP
authors.lastname: Jing
authors.affiliation: From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan 250100, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wang
authors.affiliation: From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan 250100, China.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Han
authors.affiliation: From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan 250100, China.
authors.forename: Du-Juan
authors.initials: DJ
authors.lastname: Dong
authors.affiliation: From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan 250100, China.
authors.forename: Jin-Xing
authors.initials: JX
authors.lastname: Wang
authors.affiliation: From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan 250100, China. Electronic address: xfzhao@sdu.edu.cn.
authors.forename: Xiao-Fan
authors.initials: XF
authors.lastname: Zhao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics* / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D004441:Ecdysterone / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D019476:Insect Proteins / Q000235:genetics* / Q000378:metabolism; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D008675:Metamorphosis, Biological / Q000235:genetics; D009036:Moths / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D019476:Insect Proteins; D004441:Ecdysterone; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C
keywords: CRE; cAMP response element-binding protein (CREB); cyclic AMP (cAMP); phosphorylation; protein kinase A (PKA); steroid hormone