Pertussis toxin inhibits autophosphorylation and activation of the insulin receptor kinase.
Pertussis toxin is an ADP-ribosyltransferase which alters the function of some of the GTP-binding proteins and inhibits some actions of insulin. In vivo, pertussis toxin (2 micrograms/ml/2h) inhibited insulin-stimulated tyrosyl autophosphorylation of the insulin receptor by 50% in FaO cells, and nearly completely inhibited phosphorylation of the cellular insulin receptor substrate pp185. Similarly, insulin-stimulated autophosphorylation and kinase activity of the insulin receptor purified on wheat germ agglutinin-agarose from pertussis toxin-treated FaO cells was diminished 50%; however, treatment of cells with the catalytically inactive B-oligomer of the toxin had no effect on receptor tyrosine kinase activity in vitro. Pertussis toxin did not alter insulin binding or the cellular levels of ATP, cAMP, and cGMP. Furthermore, immunoprecipitation of the insulin receptor from intact cells with anti-insulin receptor antibodies showed that pertussis toxin did not increase the phosphorylation of serine or threonine residues in the insulin receptor. These results suggest that pertussis toxin can modulate signal transduction of insulin at the level of the insulin receptor kinase.
Müller-Wieland
D
D
Klinik II und Poliklinik für Innere Medizin Universität zu Köln, FRG.
White
M F
MF
Behnke
B
B
Gebhardt
A
A
Neumann
S
S
Krone
W
W
Kahn
C R
CR
D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008114:Liver Neoplasms, Experimental; D008970:Molecular Weight; D037342:Pertussis Toxin; D010750:Phosphoproteins / Q000302:isolation & purification; D010766:Phosphorylation; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D007328:Insulin; D010750:Phosphoproteins; D010566:Virulence Factors, Bordetella; D019000:Phosphotyrosine; D014443:Tyrosine; D037342:Pertussis Toxin; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin