title: Essential role of the tyrosine kinase substrate phospholipase C-gamma1 in mammalian growth and development.
abstract: The activation of many tyrosine kinases leads to the phosphorylation and activation of phospholipase C-gamma1 (PLC-gamma1). To examine the biological function of this protein, homologous recombination has been used to selectively disrupt the Plcg1 gene in mice. Homozygous disruption of Plcg1 results in embryonic lethality at approximately embryonic day (E) 9.0. Histological analysis indicates that Plcg1 (-/-) embryos appear normal at E 8.5 but fail to continue normal development and growth beyond E 8.5-E9.0. These results clearly demonstrate that PLC-gamma1 with, by inference, its capacity to mobilize second messenger molecules is an essential signal transducing molecule whose absence is not compensated by other signaling pathways or other genes encoding PLC isozymes.
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Q S
authors.initials: QS
authors.lastname: Ji
authors.forename: G E
authors.initials: GE
authors.lastname: Winnier
authors.forename: K D
authors.initials: KD
authors.lastname: Niswender
authors.forename: D
authors.initials: D
authors.lastname: Horstman
authors.forename: R
authors.initials: R
authors.lastname: Wisdom
authors.forename: M A
authors.initials: MA
authors.lastname: Magnuson
authors.forename: G
authors.initials: G
authors.lastname: Carpenter
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005314:Embryonic and Fetal Development / Q000235:genetics*; D018390:Gene Targeting; D005838:Genotype; D006579:Heterozygote; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D051966:Phospholipase C gamma; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000201:enzymology; D013379:Substrate Specificity; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D011505:Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma