Posttranslational isoprenylation of rho protein is a prerequisite for its interaction with mastoparan and other amphiphilic agents.
The amphiphilic agents melittin, compound 48/80 and mastoparan inhibit ADP-ribosylation of porcine brain rho protein by Clostridium botulinum exoenzyme C3. However, ADP-ribosylation of recombinant rhoA expressed in E.coli was not inhibited by these agents. Accordingly, steady state GTP hydrolysis by recombinant rhoA was not stimulated by mastoparan, whereas GTP hydrolysis by porcine brain rho was stimulated 2.5-fold in the presence of this wasp venom. After microinjection of recombinant rhoA into Xenopus laevis oocytes the inhibitory effect of mastoparan on C3 ADP-ribosylation was restored. The data suggest that the amphiphilic agents tested are only active at the posttranslationally processed form of rho and that they exert their effects via the C-terminal end.
Koch
G
G
Institut für Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg, Germany.
Mohr
C
C
Just
I
I
Aktories
K
K
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism; D002250:Carbon Radioisotopes; D003001:Cloning, Molecular; D003600:Cytosol / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D045782:Hemiterpenes; D036341:Intercellular Signaling Peptides and Proteins; D008555:Melitten / Q000494:pharmacology*; D009243:NAD / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000378:metabolism*; D010455:Peptides; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D013552:Swine; D014862:Wasp Venoms / Q000494:pharmacology*; D014982:Xenopus laevis; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*; D020742:rhoA GTP-Binding Protein
D002250:Carbon Radioisotopes; D045782:Hemiterpenes; D036341:Intercellular Signaling Peptides and Proteins; D009943:Organophosphorus Compounds; D010455:Peptides; D011994:Recombinant Proteins; D014862:Wasp Venoms; D009243:NAD; D008555:Melitten; D000246:Adenosine Diphosphate Ribose; C004809:isopentenyl pyrophosphate; D003189:p-Methoxy-N-methylphenethylamine; C037500:mastoparan; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein