EPIDERMAL GROWTH-FACTOR SIGNALING AND MITOGENESIS IN PLCG1 NULL MOUSEEMBRYONIC FIBROBLASTS

Gene targeting techniques and early mouse embryos have been used to pr oduce immortalized fibroblasts genetically deficient in phospholipase C (PLC)-gamma 1, a ubiquitous tyrosine kinase substrate. Plcg1(-/-) em bryos die at embryonic day 9; however, cells derived from these embryo s proliferate as well as cells from Plcg1(+/+) embryos. The null cells do grow to a higher saturation density in serum-containing media, as their capacity to spread out is decreased compared with that of wild-t ype cells. Ln terms of epidermal growth factor receptor activation and internalization, or growth factor induction of mitogen-activated prot ein kinase, c-fos, or DNA synthesis in quiescent cells, PLcg1(-/-) cel ls respond equivalently to PLcg1(+/+) cells. Also, null cells are able to migrate effectively in a wounded monolayer. Therefore, immortalize d fibroblasts do not require PLC-gamma 1 for many responses to growth factors.