Cell Cycle

Two Mitogenic Pushes to Get to S Phase

Science's STKE  13 Feb 2001:
Vol. 2001, Issue 69, pp. tw1
DOI: 10.1126/stke.2001.69.tw1

Traversing the cell-division cycle may require more than a single exposure to growth factor. Jones and Kazlauskas suggest that the G0 to S interval may be divided into two phases, each requiring stimulation of distinct signaling events by growth factor. Serum-arrested fibroblast cells could be driven into S phase either by continuous long exposure to platelet-derived growth factor (PDGF) or by two shorter pulses of PDGF at distinct times. The first segment of the G1 phase required activation of the Erk pathway and c-Myc; the latter part of G1 required phosphatidylinositol-3-kinase activity. An analysis of growth factors that stimulate either receptor tyrosine kinases or G protein-coupled receptors revealed that exposure to different combinations of these agents in the first and second phases of the interval could also promote progression to S phase. The authors propose that the earlier biochemical events may cause accumulation of proteins that are required by the later signaling events to activate the cell-cycle machinery. Hence, there may be common mitogenic signaling pathways that different agents use to drive cell-cycle progression.

S. M. Jones, A. Kazlauskas, Growth-factor-dependent mitogenesis requires two distinct phases of signaling. Nature Cell Biol. 3, 165-172 (2001). [Online Journal]