Mastoparan, a novel mitogen for Swiss 3T3 cells, stimulates pertussis toxin-sensitive arachidonic acid release without inositol phosphate accumulation

• Published in: The Journal of cell biology Vol. 113; no. 4; pp. 943 - 950
• Main Authors: Gil, J. (Universitat de Barcelona, Hospitalet de Llobregat, Spain), Higgins, T, Rozengurt, E
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 01-05-1991; The Rockefeller University Press
• Subjects: 1-Methyl-3-isobutylxanthine - pharmacology; 3T3 cells; ACIDE ARACHIDONIQUE; ACIDO ARAQUIDONICO; ADN; Animals; Arachidonic Acid; Arachidonic Acids - metabolism; Biological and medical sciences; BIOSINTESIS; BIOSYNTHESE; Calcium - metabolism; Cell Division - drug effects; Cell growth; Cell Line; Cell physiology; Cell proliferation; Cells; Cellular signal transduction; Colforsin - pharmacology; Cultured cells; Cyclic AMP - metabolism; DNA; Down-Regulation; Drug Synergism; Enzyme Activation - drug effects; Epidermal Growth Factor - metabolism; ErbB Receptors - metabolism; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Indomethacin - pharmacology; Inositol Phosphates - metabolism; Insulin; Insulin - pharmacology; LECTINA; LECTINE; Mast cells; Mice; Mitogens - administration & dosage; Molecular and cellular biology; Peptides; Pertussis Toxin; Phosphatidylinositols - metabolism; Phosphoproteins - metabolism; Proliferació cel·lular; PROMOTEUR DE CROISSANCE; PROMOTORES DEL CRECIMIENTO; PROPIEDADES MEDICINALES; PROPRIETE PHARMACOLOGIQUE; Protein Kinase C - metabolism; Signal Transduction; Swiss 3T3 cells; Toxins; Transducció de senyal cel·lular; Type C Phospholipases - metabolism; VENENOS; VENIN; VESPIDAE; Virulence Factors, Bordetella - pharmacology; Wasp Venoms - pharmacology; Whooping cough; Vertebrata; Mammalia; Mouse; Rodentia; 3T3-Cell line; Stimulation; Inositol phosphate; Biological accumulation; Arachidonic acid; Release
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.113.4.943

Mastoparan, a basic tetradecapeptide isolated from wasp venom, is a novel mitogen for Swiss 3T3 cells. This peptide induced DNA synthesis in synergy with insulin in a concentration-dependent manner; half-maximum and maximum responses were achieved at 14 and 17 micromole, respectively. Mastoparan also stimulated DNA synthesis in the presence of other growth promoting factors including bombesin, insulin-like growth factor-1, and platelet-derived growth factor. The synergistic mitogenic stimulation by mastoparan can be dissociated from activation of phospholipase C. Mastoparan did not stimulate phosphoinositide breakdown, Ca2+ mobilization or protein kinase C-mediated phosphorylation of a major cellular substrate or transmodulation of the epidermal growth factor receptor. In contrast, mastoparan stimulated arachidonic acid release, prostaglandin E2 production, and enhanced cAMP accumulation in the presence of forskolin. These responses were inhibited by prior treatment with pertussis toxin. Hence, mastoparan stimulates arachidonic acid release via a pertussis toxin-sensitive G protein in Swiss 3T3 cells. Arachidonic acid, like mastoparan, stimulated DNA synthesis in the presence of insulin. The ability of mastoparan to stimulate mitogenesis was reduced by pertussis toxin treatment. These results demonstrate, for the first time, that mastoparan stimulates reinitiation of DNA synthesis in Swiss 3T3 cells and indicate that this peptide may be a useful probe to elucidate signal transduction mechanisms in mitogenesis