Cholera toxin can ADP-ribosylate Gs as well as Gi in ACTH-unresponsive human adrenocortical cancer.
It is well known that cholera toxin (CT) stimulates ADP-ribosylation of Gs and also pertussis toxin (PT) does Gi. Each GTP-binding protein has its own action in the regulation of adenylate cyclase. A human non-functioning adrenocortical cancer tissue showed an unresponsiveness in adenylate cyclase to ACTH although ACTH and CT activated adenylate cyclase in a non-functioning adrenal adenoma tissue. CT ADP-ribosylated 43 kDa protein of the plasma membrane of the cancer tissue while CT and PT could ADP-ribosylate 43 kDa and 38 kDa protein in the adenoma tissue, respectively. Immunoblotting analysis of the cancer tissue demonstrated that 40 kDa protein was detected by anti-Gs antibody as well as by anti-Gi antibody. The present experiments demonstrated that CT could ADP-ribosylate Gs which has stimulatory action on adenylate cyclase and also Gi which inhibits adenylate cyclase. Thus it is suggested that CT can activate the ADP-ribosylation of Gs and also Gi in a human adrenocortical cancer tissue, partly resulting in abnormal regulation of adenylate cyclase which may be crossly related to ACTH-unresponsiveness.
Nishikawa
T
T
Department of Medicine, Yokohama Rosai Hospital, Japan.
Yoshida
A
A
Omura
M
M
Sasano
H
H
Noda
M
M
D000236:Adenoma / Q000378:metabolism*; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D000306:Adrenal Cortex Neoplasms / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology*; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D037342:Pertussis Toxin; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D000324:Adrenocorticotropic Hormone; D002772:Cholera Toxin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases