Epidermal growth factor signaling and mitogenesis in Plcg1 null mouse embryonic fibroblasts.
Gene targeting techniques and early mouse embryos have been used to produce immortalized fibroblasts genetically deficient in phospholipase C (PLC)-gamma1, a ubiquitous tyrosine kinase substrate. Plcg1(-/-) embryos die at embryonic day 9; however, cells derived from these embryos 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-type cells. In terms of epidermal growth factor receptor activation and internalization, or growth factor induction of mitogen-activated protein kinase, c-fos, or DNA synthesis in quiescent cells, PLcg1(-/-) cells respond equivalently to PLcg1(+/+) cells. Also, null cells are able to migrate effectively in a wounded monolayer. Therefore, immortalized fibroblasts do not require PLC-gamma1 for many responses to growth factors.
Ji
Q S
QS
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA.
Ermini
S
S
Baulida
J
J
Sun
F L
FL
Carpenter
G
G
D000818:Animals; D002455:Cell Division; D002465:Cell Movement; D004622:Embryo, Mammalian / Q000166:cytology*; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D051966:Phospholipase C gamma; D010766:Phosphorylation; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000235:genetics* / Q000378:metabolism
D007527:Isoenzymes; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D010738:Type C Phospholipases; D051966:Phospholipase C gamma