title: Regulation and physiological functions of mammalian phospholipase C.
abstract: Phospholipase C (PLC) is a key enzyme in phosphoinositide metabolism. PLC hydrolyses phosphatidylinositol 4,5-bis-phosphate to generate two second messengers, inositol 1,4,5-trisphosphate and diacylglycerol, that generate diverse cellular responses. PLC is activated by various signalling molecules, including Ca2+, heterometric G proteins, small G proteins, and receptor/non-receptor tyrosine kinases. In addition to their enzymatic activity, some PLC subtypes also function as a guanine nucleotide exchange factor, GTPase-activating protein, and adaptor protein, independent of their lipase activity. There are 13 PLC isozymes in mammals, and they are categorized into six classes based on structure. Generation and analysis of genetically modified mice has revealed the unexpectedly diverse physiological functions of PLC isozymes. Although all PLC isozymes catalyze the same reaction, each PLC isozyme has unique physiological functions. This review focuses on the regulation and physiological functions of PLCs.
authors.affiliation: Laboratory of Genome and Biosignals, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.|AMED-CREST, Japan Agency for Medical Research and Development, Tokyo, Japan.|PRIME, Japan Agency for Medical Research and Development, Tokyo, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Laboratory of Genome and Biosignals, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.|AMED-CREST, Japan Agency for Medical Research and Development, Tokyo, Japan.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Fukami
mesh_terms: D000818:Animals; D004075:Diglycerides / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*
chemical_list: D004075:Diglycerides; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D007527:Isoenzymes; D019269:Phosphatidylinositol 4,5-Diphosphate; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases
keywords: Ca2+; G protein; Genetically modified mice; PLC; tyrosine kinase