Involvement of farnesyl protein transferase (FPTase) in FcarepsilonRI-induced activation of RBL-2H3 mast cells.
Changes in farnesyl protein transferase (FPTase) activity and FPTase beta-subunit protein levels were determined in IgE-sensitized RBL-2H3 mast cells in response to polyvalent antigen administration. Ten minutes after the addition of DNP modified BSA to mast cells, whose high affinity receptor for IgE (FcvarepsilonRI) contained bound anti-DNP IgE, FPTase specific activity increased by 54 +/- 28%. Time course studies showed FPTase specific activity doubled during a 20- to 30-min period after antigen-induced cell aggregation. Also, an increase in FPTase beta-subunit protein during this time ( approximately 30%) was observed; this protein increase was not accompanied by a similar increase in FPTase beta-subunit m-RNA levels. The FcvarepsilonRI aggregation had no significant effect on the activities of other enzymes involved with farnesyl diphosphate (FPP) metabolism: FPP synthase, isopentenyl diphosphate isomerase, geranylgeranyl protein transferase, and squalene synthase. Specific inhibition of FPTase activity by manumycin was studied to determine what role FPTase plays in mast cell activation. Manumycin profoundly inhibited hexosaminidase release in activated cells, indicating FPTase is required for signal transduction involved with protein exocytosis from RBL-2H3 mast cells.
Chen
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F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, 20814-4799, USA.
Mehan
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Gupta
S D
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Goldberg
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Shechter
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I
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D015152:Blotting, Northern; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008407:Mast Cells / Q000502:physiology*; D011090:Polyenes / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger / Q000502:physiology; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D011090:Polyenes; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase; C054474:manumycin