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. 1985 Nov;4(11):2927–2932. doi: 10.1002/j.1460-2075.1985.tb04025.x

alpha-Thrombin-induced early mitogenic signalling events and G0 to S-phase transition of fibroblasts require continual external stimulation.

E Van Obberghen-Schilling, J C Chambard, S Paris, G L'Allemain, J Pouysségur
PMCID: PMC554600  PMID: 2998766

Abstract

In resting Chinese hamster fibroblasts (CCL39) alpha-thrombin rapidly stimulates several biochemical events implicated in the mitogenic response, including the breakdown of inositol phospholipids, activation of a plasma membrane Na+/H+ antiporter, phosphorylation of ribosomal protein S6 and increased expression of the proto-oncogene c-myc. Complete removal of the growth factor during cellular G0/G1 transit precludes the re-initiation of DNA synthesis. The present study was designed to examine the fate of alpha-thrombin-activated early events following growth factor inactivation. In cells stimulated for 30 min with alpha-thrombin, neutralization of the growth factor results in: (i) immediate arrest of inositol phosphate formation, (ii) rapid inactivation of Na+/H+ exchange, (iii) deactivation of the S6 phosphorylating system and (iv) strong reduction of c-myc mRNA level. Our findings that commitment for DNA synthesis as well as persistent activation of 'early' cellular events requires continual growth factor stimulation suggest that: (i) growth factor-induced transmembrane signals have a short life and (ii) the generation of these signals during the 8 h of the pre-replicative phase is required for G0-arrested cells to enter the S phase.

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Selected References

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