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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:1830-1836.)
© 1997 American Heart Association, Inc.

Articles

Signal Transduction Through Trimeric G Proteins in Megakaryoblastic Cell Lines

Hans van der Vuurst; Gijsbert van Willigen; Anke van Spronsen; Maaike Hendriks; José Donath; ; Jan-Willem N. Akkerman

From the Department of Hematology, University Hospital Utrecht, Netherlands.

Correspondence to Dr J.W.N. Akkerman, University Hospital Utrecht, Department of Hematology (G03.647), PO Box 85.500, 3508 GA Utrecht, The Netherlands. E-mail J.W.N.Akkerman{at}lab.azu.nl

Abstract The biogenesis of trimeric G proteins was investigated by measurement of the expression of -subunits in the megakaryoblastic cell lines MEG-01, DAMI, and CHRF-288-11, representing stages of increasing maturation, and compared with platelets. Megakaryoblasts and platelets contained approximately equal amounts of G_i-1/2, G_i-3, G_q, and G₁₂ protein. Maturation was accompanied by (1) downregulation of mRNA for G_s and disappearance of iloprost-induced Ca²⁺ mobilization, (2) upregulation of the long form of G_s protein (G_s-L) and an increase in iloprost-induced cAMP formation, and (3) upregulation of G₁₆ mRNA and G₁₆ protein and appearance of thromboxane A₂-induced signaling (Ca²⁺ mobilization and stimulation of prostaglandin I₂–induced cAMP formation). G_z protein was absent in the megakaryoblasts despite weak expression of G_z mRNA in DAMI and relatively high levels of G_z mRNA and G_z protein in platelets. These findings reveal major changes in G protein–mediated signal transduction during megakaryocytopoiesis and indicate that G₁₆ couples the thromboxane receptor to phospholipase C_ß.

Key Words: megakaryocytes • platelets • signal transduction • G protein

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