Heterotrimeric G-protein candidates for Ge in the ACTH secretory pathway.
The mouse AtT-20/D16-16 anterior pituitary tumour cell line was used to identify candidate heterotrimeric G-proteins for G-exocytosis (Ge) which mediates calcium ion-stimulated adrenocorticotrophin (ACTH) secretion in this cell line. AtT-20 cells express several heterotrimeric G-protein alpha subunits; Gs alpha, Gt alpha, Gq alpha, G11alpha, G12alpha, G13alpha, G14alpha, G15alpha, Gz alpha, Gi2alpha, Gi3alpha, and Go alpha and so heterotrimeric G-protein selective agents were used to differentiate between these candidates. Agents which stimulate ACTH secretion via Ge were not pertussis toxin (PTX)-sensitive nor was cholera toxin (CTX) able to stimulate ACTH secretion from permeabilised cells in the absence of calcium. G-protein antagonists which inhibit activation of Gs, Gi, and Gq subfamilies did not attenuate Ge-stimulated ACTH secretion from permeabilised AtT-20 cells. In AtT-20 cells the stimulatory G-protein involved in the late stages of the ACTH secretory pathway does not belong to the Gs, Gi (with the exception of Gz) or Gq subfamilies of heterotrimeric G-proteins leaving Gz, G12 or G13 as the strongest candidates for Ge.
Molecular Endocrinology Group, School of Biological and Medical Sciences, University of St Andrews, UK.
R
R
Erlich
B W
BW
McFerran
D M
DM
Felstead
S B
SB
Guild
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D005089:Exocytosis; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D008297:Male; D051379:Mice; D010455:Peptides; D037342:Pertussis Toxin; D010903:Pituitary Gland, Anterior; D010911:Pituitary Neoplasms; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014862:Wasp Venoms / Q000494:pharmacology
D036341:Intercellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D010455:Peptides; D010566:Virulence Factors, Bordetella; D014862:Wasp Venoms; D005576:Colforsin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D013004:Somatostatin; C037500:mastoparan; D000324:Adrenocorticotropic Hormone; D002772:Cholera Toxin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002118:Calcium