Control of late G0/G1 progression and protein modification by SmC/IGF I.
Somatomedin C/insulin-like growth factor I (SmC/IGF I) mediates traverse of late G0/G1 in density-arrested BALB/c-3T3 cells from a distinct growth arrest point in mid-G0/G1 (the V point) to the initiation of DNA synthesis. As a prelude to future studies aimed at defining the mechanism of action of SmC/IGF I, we investigated the level (e.g., transcriptional, translational) at which SmC/IGF I modulates V to S traverse. The post-V point progression of cells arrested at the V point by amino acid starvation and released into amino acid-replenished medium containing SmC/IGF I, insulin, or platelet-poor plasma (PPP) did not require either mRNA synthesis or an increase in the overall level of protein synthesis. Although two-dimensional gel analysis of proteins prepared from SmC/IGF I-treated cells did not reveal any preferentially synthesized proteins, several SmC/IGF I-induced protein modifications, which result in an increase in isoelectric point (pI) and occur in the absence of mRNA synthesis, were evident. These findings suggest that SmC/IGF I modulates late G0/G1 progression by a posttranscriptional process that may involve protein modification.
Olashaw
N E
NE
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Van Wyk
J J
JJ
Pledger
W J
WJ
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D004261:DNA Replication / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007399:Interphase; D007526:Isoelectric Point; D051379:Mice; D008807:Mice, Inbred BALB C; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D013002:Somatomedins / Q000494:pharmacology*; D014529:Uridine / Q000378:metabolism
D000596:Amino Acids; D007328:Insulin; D011506:Proteins; D012333:RNA, Messenger; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D014529:Uridine