Changes of the phosphorylation of membrane-associated proteins following treatment of HeLa cells with the guanine analogue, queuine.
The guanine analogue, queuine (q), is a nutrition factor for eukaryotes and occurs as a free base or as modified nucleoside queuosine (Q) inserted into the anticodon of tRNAs(GUN) in place of guanosine (G). The free q-base and the corresponding Q-deficient tRNAs accumulate in fast proliferating tumors and in embryonic cells. The present data show that treatment of Q-deficient HeLa cells with queuine resulted in reduced in vitro phosphorylation of two membrane-associated proteins, pp110 and pp18. Reduced phosphorylation of pp110 and pp18 was also observed when a membrane-containing particulate fraction from queuine starved HeLa cells was labelled with [gamma-32P]ATP in the presence of queuine. Incorporated phosphate into pp110 was alkali-stable, suggesting that this protein became phosphorylated at tyrosine residues. After stimulation of intact Q-deficient cells with epidermal growth factor, pp110 was rapidly phosphorylated at tyrosine residues. The results show that queuine as a free base influences protein tyrosine phosphorylation in intact cells, suggesting that it might interfere with protein phosphorylation involved in signal transduction pathways.
Langgut
W
W
Institut für Biochemie/Medizinische Fakultät, Universität Erlangen-Nürnberg, Germany.
D000255:Adenosine Triphosphate / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine; D015398:Signal Transduction; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D008565:Membrane Proteins; D010750:Phosphoproteins; D019000:Phosphotyrosine; D014443:Tyrosine; D006147:Guanine; D004815:Epidermal Growth Factor; C019549:queuine; D000255:Adenosine Triphosphate