Transmembrane signalling pathways initiating cell growth in fibroblasts

Publisher Website
Google Scholar
Abstract
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, x-thrombin (THR), serotonin (5-HT) and insulin. THR and 5-HT stimulate, via a G-protein (G p ), a polyphosphoinositide-specific phospholipase C (PtdIns(4,5)P 2 -PLC). In contrast, the mitogens EGF, FGF, PDGF, and insulin do not stimulate PtdIns(4,5)P 2 -PLC, unless this pathway has been preactivated by THR or AIF 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 Gproteins involved in signalling growth: G p , coupling receptors to PtdIns(4,5)P 2 -PLC, and G 1 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 G p - and G i -mediated actions; and (iii) tyrosine kinases positively ‘cross-communicate ’ with the inositol-lipid pathway (phosphorylation of G p , PLC, Ptdlns kinases...?).