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Query: EC:3.1.4.3 (
phospholipase C
)
18,461
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
PLC (
phospholipase C
) isoenzymes catalyse the conversion of PtdIns(4,5)P2 into the Ca2+-mobilizing second messenger, Ins(1,4,5)P3, and the protein kinase C-activating second messenger, diacylglycerol. With the goal of identifying additional mammalian PLC isoenzymes, we screened the NCBI non-redundant database using a BLAST algorithm for novel sequences with homology with the conserved PLC catalytic core. Two unique sequences corresponding to two unknown PLC isoenzymes were identified, and one of these, designated
PLC-eta2
, was cloned and characterized. Most of the coding sequence of
PLC-eta2
was constructed from two ESTs (expressed sequence tags), which included an overlapping sequence that was confirmed by multiple ESTs and mRNAs. 5'-RACE (rapid amplification of cDNA ends) also identified an upstream exon not deduced from available EST or mRNA sequences. Sequence analysis of
PLC-eta2
revealed the canonical domains of a PLC isoenzyme with an additional long C-terminus that contains a class II PDZ-binding motif. Genomic analyses indicated that
PLC-eta2
is encoded by 23 exons. RT-PCR (reverse transcriptase-PCR) analyses illustrated expression of
PLC-eta2
in human retina and kidney, as well as in mouse brain, eye and lung. RT-PCR with exon-specific primers also revealed tissue-specific expression of four splice variants in mouse that represent alternative use of sequences in exons 21, 22 and 23.
PLC-eta2
-specific antisera recognized one of these splice variants as an approx. 155 kDa species when expressed in COS-7 cells;
PLC-eta2
natively expressed in 1321N1 human astrocytoma cells also migrated as an approx. 155 kDa species. PLC activity was observed in vitro and in vivo for three different constructs of
PLC-eta2
, each containing possible alternatively spliced first exons. Co-expression of
PLC-eta2
with Gbeta1gamma2 dimers of heterotrimeric G-proteins resulted in marked stimulation of inositol lipid hydrolysis. Thus
PLC-eta2
may in part function downstream of G-protein-coupled receptors.
...
PMID:Molecular cloning and characterization of PLC-eta2. 1623 48
A study in this issue of the Biochemical Journal by Harden and colleagues, in association with one published in the Biochemical Journal very recently [Hwang, Oh, Shin, Kim, Ryu and Suh (2005) Biochem. J. 389, 181-186], have defined a new member of the superfamily of PLC (phosphoinositide-specific
phospholipase C
) enzymes, PLCeta. Two isoforms, PLCeta1 and
PLCeta2
, and their splice variants add to the molecular diversity of PLC enzymes. The studies of PLCeta regulation suggest that at least some splice variants of
PLCeta2
could be regulated by the G-protein subunits Gbetagamma. As two other families, PLCbeta and PLC, are also regulated through heterotrimeric G-proteins, this finding reveals further complexity and possible interplay between different PLC families and their regulatory networks. At this point, when it is likely that the PLCeta family completes the effort of identifying new members of this related group of PLC enzymes, I also discuss some more general concepts of PLC regulation and catalysis, and challenges awaiting their further studies.
...
PMID:New insights into the families of PLC enzymes: looking back and going forward. 1610 6
Phosphoinositol-specific
phospholipase C
enzymes (PLCs) are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C activation. A sixth class of phosphoinositol-specific PLC with a novel domain structure, PLC-eta (PLCeta) has recently been discovered in mammals. Recent research, reviewed here, shows that this class consists of two enzymes, PLCeta1 and
PLCeta2
. Both enzymes hydrolyze phosphatidylinositol 4,5-bisphosphate and are more sensitive to Ca2+ than other PLC isozymes and are likely to mediate G-protein-coupled receptor (GPCR) signalling pathways. Both enzymes are expressed in neuron-enriched regions, being abundant in the brain. We demonstrate that they are also expressed in neuroendocrine cell lines. PLCeta enzymes therefore represent novel proteins influencing intracellular Ca2+ dynamics and protein kinase C activation in the brain and neuroendocrine systems as putative mediation of GPCR regulation.
...
PMID:Phospholipase C-eta enzymes as putative protein kinase C and Ca2+ signalling components in neuronal and neuroendocrine tissues. 1789 20
