title: Inhibition of tyrosine phosphorylation blocks hormone-stimulated calcium influx in an insect steroidogenic gland.
abstract: In the tobacco hornworm Manduca sexta (M. sexta) as in other insects, ecdysone synthesis occurs in the prothoracic glands and is stimulated by the brain neuropeptide prothoracicotropic hormone (PTTH). PTTH activates the prothoracic glands through the second messenger cAMP, the synthesis of which is stimulated by calcium. We previously found that the Src kinase inhibitor 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-D]-pyrimidine (PP1) inhibits PTTH-stimulated cAMP synthesis and ecdysone secretion. In the present study, we show that by contrast, PP1 does not block cAMP synthesis stimulated by the calcium ionophore A23187, and that PP1 augments A23187-stimulated ecdysone secretion. Hence, once glandular levels of calcium are elevated, Src family kinase activity is no longer needed for, and may actually inhibit, steroidogenesis. PP1 blocks calcium influx in PTTH-stimulated prothoracic glands, indicating that tyrosine phosphorylation by a member of the Src kinase family is required for calcium influx. These results suggest that prothoracic gland calcium channels are regulated either directly or indirectly by tyrosine phosphorylation.
authors.affiliation: Department of Biology, 433 Richards Hall, Northeastern University, 360 Huntington Ave, Boston, MA 02115, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Priester
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Smith
mesh_terms: D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004440:Ecdysone / Q000378:metabolism; D004702:Endocrine Glands / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007301:Insect Hormones / Q000494:pharmacology*; D007476:Ionophores / Q000494:pharmacology; D007814:Larva / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D018402:Manduca / Q000737:chemistry*; D009479:Neuropeptides / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects*; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C108123:4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine; D004791:Enzyme Inhibitors; D007301:Insect Hormones; D007476:Ionophores; D009479:Neuropeptides; D011720:Pyrazoles; D011743:Pyrimidines; D011994:Recombinant Proteins; D004440:Ecdysone; D000001:Calcimycin; D014443:Tyrosine; C009089:prothoracicotropic hormone; D000242:Cyclic AMP; D019061:src-Family Kinases; D002118:Calcium