Transmembrane signalling pathways initiating cell growth in fibroblasts.
The mechanisms of growth factor action were studied in a fibroblastic cell line capable of reversible growth arrest in G0-G1. This cell line, derived from Chinese hamster lung, can be stimulated to divide by a limited set of purified growth factors, including EGF, FGF, PDGF, alpha-thrombin (THR), serotonin (5-HT) and insulin. THR and 5-HT stimulate, via a G-protein (Gp), a polyphosphoinositide-specific phospholipase C (PtdIns(4,5)P2-PLC). In contrast, the mitogens EGF, FGF, PDGF, and insulin do not stimulate PtdIns(4,5)P2-PLC unless this pathway has been preactivated by THR or AlF-4. Finally, from the specific inhibitory action of pertussis toxin on THR- and 5-HT-induced DNA synthesis, and from the exploitation of the 5-HT pharmacological tools, we conclude that: (i) there are at least two distinct G-proteins involved in signalling growth: Gp, coupling receptors to PtdIns(4,5)P2-PLC, and Gi, coupling receptors negatively to adenylyl cyclase and probably to other unknown effector(s); (ii) activation of receptor-tyrosine kinases provides an alternate growth factor signalling pathway, independent of Gp- and Gi-mediated actions; and (iii) tyrosine kinases positively 'cross-communicate' with the inositol-lipid pathway (phosphorylation of Gp, PLC, PtdIns kinases...?).
Pouysségur
J
J
Centre de Biochimie, Université de Nice, France.
Chambard
J C
JC
L'Allemain
G
G
Magnaldo
I
I
Seuwen
K
K
D000818:Animals; D002450:Cell Communication; D002455:Cell Division; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D006133:Growth Substances / Q000494:pharmacology
D006133:Growth Substances