Disease relevance of PLC1

• A simple and reliable method for rapid production and purification of Pseudomonas aeruginosa haemolytic phospholipase C [1].
• Other phospholipase C-producing genera and their numbers were Acinetobacter, two; Alcaligenes, three; Bacillus, two; Citrobacter, one; Enterobacter, three; and Flavobacterium, two [2].
• While ammonium sulphate purification requires large amounts of bacterial suspensions and leads to low yields, production of recombinant protein in Escherichia coli is no more successful because of frequent inclusion bodies and accumulation of inactive PLC in the periplasmic space [1].
• A phospholipase C from the Dallas 1E strain of Legionella pneumophila serogroup 5: purification and characterization of conditions for optimal activity with an artificial substrate [3].
• High-level expression of recombinant phospholipase C from Bacillus cereus in Pichia pastoris and its characterization [4].

High impact information on PLC1

• Structure, function, and control of phosphoinositide-specific phospholipase C [5].
• Phosphoinositide-specific phospholipase C (PLC) subtypes beta, gamma, and delta comprise a related group of multidomain phosphodiesterases that cleave the polar head groups from inositol lipids [5].
• ABP1p is a novel protein with a 50 amino-acid C-terminal domain that is very similar to the SH3 domain in the non-catalytic region of nonreceptor tyrosine kinases (including those encoded by the proto-oncogenes c-src and c-abl), in phospholipase C gamma and in alpha-spectrin [6].
• Phospholipase C and two inositol polyphosphate (IP) kinases constitute a signaling pathway that regulates nuclear messenger RNA export through production of inositol hexakisphosphate (IP6) [7].
• Here, we show that in native cardiac cells and heterologous expression systems, G alpha q-linked receptors or tyrosine kinase receptors that activate PLC potently inhibit channel activity [8].

Chemical compound and disease context of PLC1

• Phospholipase C from the Dallas 1E strain of Legionella pneumophila serogroup 5 was purified from buffered yeast extract culture supernate by ion-exchange chromatography followed by fractionation by manganous chloride and ammonium sulphate precipitation steps [3].

Biological context of PLC1

• Deletion of PLC1 results in nocodazole sensitivity, mitotic delay, and a higher frequency of chromosome loss [9].
• No inositol triphosphate receptor homologue has been identified in the S. cerevisiae genome; and, therefore, the transduction mechanism from Plc1 activation to calcium flux generation still has to be identified [10].
• The Saccharomyces cerevisiae PLC1 gene encodes a homolog of the delta isoform of mammalian phosphoinositide-specific phospholipase C. Cells deleted for PLC1 ( plc1Delta) are viable, but display several phenotypes, including osmotic, temperature, and nocodazole sensitivity [11].
• Genetic evidence for a role of phospholipase C at the budding yeast kinetochore [9].
• Disruption of PLC1 results in slow growth or lethality for cells, depending on their genetic background and the medium, indicating that PLC1 is important for cell growth [12].

Anatomical context of PLC1

• Yeast cells lacking the PLC1 gene have many small vacuoles, indicating defects in protein trafficking to the vacuole or vacuole fusion, and purified Plc1p stimulates vacuole fusion [13].
• Immunoblot analysis of the cell fractions prepared from transgenic tobacco plants over-expressing the FLAG epitope-tagged PI-PLC1 fusion protein indicated that the protein encoded by the PI-PLC1 cDNA was localized in the cytosol and plasma membrane [14].
• In addition, the yeast PLC1 deletion mutant lacking phosphoinositide-specific phospholipase C, a key enzyme for generating Ca2+ signals in higher eukaryotic cells, responds normally to the pheromone [15].
• The yeast and mammalian isoforms of phosphatidylinositol transfer protein can all restore phospholipase C-mediated inositol lipid signaling in cytosol-depleted RBL-2H3 and HL-60 cells [16].
• Activation and localization of inositol phosphosphingolipid phospholipase C, Isc1p, to the mitochondria during growth of Saccharomyces cerevisiae [17].

Associations of PLC1 with chemical compounds

• Similarly, the presence of a membrane stabilizer (sorbitol) or the loss of phosphatidylinositol-specific phospholipase C (PLC1) protects Ume3p from oxidative-stress-induced degradation [18].
• IP(3) accumulation upon glucose addition was completely absent in the plc1Delta strain and was amplified both by deletion of either ARG82 or IPK1 genes and by overexpression of PLC1 [10].
• We have shown previously that in budding yeast, Plc1p (phosphoinositide-specific phospholipase C) localizes to centromeric loci, associates with the kinetochore proteins Ndc10p and Cep3p, and affects the function of kinetochores [9].
• DAG underwent ATP-dependent turnover during vacuole fusion, but was replenished by the hydrolysis of phosphatidylinositol 4,5-bisphosphate to DAG by PLC [13].
• Using [3H]phytosphingosine and [3H]inositol-labeled yeast sphingolipids, a novel membrane-associated phospholipase C-type activity that generated ceramide from inositol-P-ceramide, mannosylinositol-P-ceramide, and mannose(inositol-P)2-ceramide was demonstrated [19].

Physical interactions of PLC1

• Phospholipase C binds to the receptor-like GPR1 protein and controls pseudohyphal differentiation in Saccharomyces cerevisiae [20].
• Phosphoinositide-specific phospholipase C interacts with phosphatidylinositol kinase homolog TOR2 [21].

Regulatory relationships of PLC1

• Finally, a ume3 null allele suppresses the growth defect of plc1 mutants in response to either elevated temperature or the presence of hydrogen peroxide [18].

Other interactions of PLC1

• Oxidative stress-induced destruction of the yeast C-type cyclin Ume3p requires phosphatidylinositol-specific phospholipase C and the 26S proteasome [18].
• Surprisingly, overexpression of PLC1 and MSS4 also suppressed the growth defect of a class B mutant [22].
• The hormone receptor-like protein Gpr1p physically interacts with phosphatidylinositol-specific phospholipase C (Plc1p) and with the Galpha protein Gpa2p, as shown by two-hybrid assays and co-immune precipitation of epitope-tagged proteins [20].
• Deletion of PLC1, as well as plc1 mutations which abrogate the interaction of Plc1p with the CBF3 complex, results in a higher frequency of minichromosome loss, nocodazole sensitivity, and mitotic delay [23].
• Furthermore, deletion of PLC1 in an inp51 mutant does not abrogate cold tolerance, indicating that Plc1p-mediated production of soluble inositol phosphates is not required [24].

Analytical, diagnostic and therapeutic context of PLC1

• The polymerase chain reaction was used to isolate a Saccharomyces cerevisiae gene (PLC1) that encodes a protein of 869 amino acids (designated Plc1p) that bears greatest resemblance to the delta isoforms of mammalian PI-PLC in terms of overall sequence similarity and domain arrangement [25].
• Molecular cloning of the plc1+ gene of Schizosaccharomyces pombe, which encodes a putative phosphoinositide-specific phospholipase C [26].

References