Disease relevance of PLCB1

• Recombinant turkey PLC-beta was purified to homogeneity following expression from a recombinant baculovirus in Sf9 insect cells [1].
• The identification of the PLC beta isozyme present in human myocardium and the understanding of its regulation by G protein subunits sets the stage for the investigation of possible involvement of this system in the pathophysiology of myocardial hypertrophy [2].
• The effect of beta gamma subunits may provide a pathway for the regulation of PLC beta isozymes by pertussis toxin-sensitive G proteins or may indicate that the alpha subunit of Gq and its associated beta gamma both participate in regulation of the same phospholipase molecule [3].
• Small cell lung carcinoma exhibits greater phospholipase C-beta1 expression and edelfosine resistance compared with non-small cell lung carcinoma [4].
• Both PLC-beta 1 and PLC-beta 2 were purified from extracts of HeLa cells that had been transfected with vaccinia virus containing the corresponding cDNAs [5].

Psychiatry related information on PLCB1

• No modifications in PLCbeta1 solubility in PBS-, deoxycholate- and sodium dodecylsulphate-soluble fractions have been observed in CJD when compared with controls [6].

High impact information on PLCB1

• Addition of PLC-beta 1 caused a rapid burst of hydrolysis of Gq/11-bound GTP that was at least 50-fold faster than in its absence [7].
• Thus, PLC-beta 1 stimulates hydrolysis of Gq/11-bound GTP and acts as a GTPase-activating protein (GAP) for its physiologic regulator, Gq/11 [7].
• Determination of the primary structure of PLC-154 demonstrates diversity of phosphoinositide-specific phospholipase C activities [8].
• Regions of homology between PLC-154 and the previously described PLC-148 allow the assignment of a putative catalytic domain to the central region of PLC-154 [8].
• NHERF2 simultaneously binds phospholipase C beta 1 and an atypical, carboxyl-terminal PDZ consensus motif, ETVM, of the PTH1R through PDZ1 and PDZ2, respectively [9].

Chemical compound and disease context of PLCB1

• The levels of expression of phosphoinositide-specific phospholipase Cs (PLCs) were examined in a series of primary human colon carcinomas and in eight colon carcinoma cell lines by using monoclonal antibodies and cDNA probes for PLC gamma 1, PLC beta 1, and PLC delta 1 [10].
• Densitometric analysis of the bands demonstrated decreased expression levels of PLCbeta1 and PLCgamma, a non-related phospholipase which is a substrate of tyrosine kinase, in CJD cases when compared with controls [6].
• PLC-I mRNA levels are extremely high in brain and rat C6 glioma cells with lower levels in other tissues tested [11].
• Abnormal metabotropic glutamate receptor expression and signaling in the cerebral cortex in diffuse Lewy body disease is associated with irregular alpha-synuclein/phospholipase C (PLCbeta1) interactions [12].
• Similarly, calcium mobilization is Galpha(q)-mediated and independent of Galpha(i/o) and Galpha(12/13) because pertussis toxin Y-27632 and had no effect, whereas U-73122 inhibition of phospholipase C-beta blocked the response [13].

Biological context of PLCB1

• Consistently, LPA(2)-mediated PLC-beta activation was specifically inhibited by the gene silencing of PLC-beta3 [14].
• Among the phospholipase C that catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate, four mammalian phospholipase C-beta (PLC-beta) isotypes (isotypes 1-4) are activated through G protein-coupled receptors (GPCRs) [15].
• In addition, we provide evidence consistent with the existence of PLC-beta homodimers in a whole-cell context, using fluorescent protein-tagged constructs and microscopic fluorescence resonance energy transfer assays [16].
• These data suggest that signal transduction through the TxA2 receptor is affected by decreased activity of Gq in platelets of neonates, and that this defect in signal transduction through PLC beta contributes to the observed poor response of newborns' platelets to TxA2 and consequently to TxA2-dependent agonists such as collagen [17].
• Reverse transcriptions and polymerase chain reactions (RT-PCR) provided evidence for PLC beta 1 mRNA being expressed in human myocardium, whereas PCR products corresponding to PLC beta 2 and PLC beta 3 mRNAs were not detected [2].

Anatomical context of PLCB1

• Interestingly, NHERF2 potentiated the PLC-beta activation by carbachol in COS7 and HeLa cells, while mutant NHERF2, lacking the second PDZ domain, had no such effect [15].
• The results of Western blotting analysis with various antibodies against PLC isozymes showed that peak-Ia (PLC-delta type), peak-Ib (PLC-gamma 1 type), and peak-IIc (PLC-beta type) and two unidentified activity peaks (PLC-IIa and PLC-IIb) were present in human platelet cytosol [18].
• Reconstitution of thromboxane A2 receptor-stimulated phosphoinositide hydrolysis in isolated platelet membranes: involvement of phosphoinositide-specific phospholipase C-beta and GTP-binding protein Gq [19].
• The immunoreactivity and mobility on SDS/PAGE of the recombinant enzyme were the same as observed with native turkey erythrocyte PLC-beta [1].
• The aim of the present study was to identify and to characterize the PLC beta isoform present in human myocardium [2].

Associations of PLCB1 with chemical compounds

• In this report, we show that EBP50 inhibits the phospholipase C (PLC)-beta-mediated inositol phosphate production of a Galpha(q)-coupled receptor as well as PLC-beta activation by the constitutively active Galpha(q)-R183C mutant [20].
• Anti-Gq antibody, but not anti-Gi2 or Gi3 antibody, inhibited both GTP[S]- and GTP/U46619-dependent reconstitution of phosphoinositide hydrolysis with phospholipase C-beta [19].
• In contrast, only phospholipase C-beta was able to reconstitute GTP-dependent U46619-induced hydrolysis [19].
• Moreover, the catalytic activities of the recombinant enzyme were indistinguishable from those of native turkey erythrocyte PLC-beta in assays carried out in the presence of cholate and Ca2+, or in assays of activity after reconstitution with G alpha 11 or G-protein beta gamma-subunits [1].
• Heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins) of the Gq subfamily activate the PLC beta 1 isoform of PLC [3].

Physical interactions of PLCB1

• The PH delta PLC beta chimera showed PI(4,5)P2-dependent membrane binding similar to PLC delta 1 and a G beta gamma interaction energy close to that of PLC delta 1 [21].
• Role of the gamma subunit prenyl moiety in G protein beta gamma complex interaction with phospholipase Cbeta [22].

Regulatory relationships of PLCB1

• We also demonstrate that EBP50 inhibits Galpha(q) signaling by preventing the interaction between Galpha(q) and the TP receptor and between activated Galpha(q) and PLC-beta1 [20].
• Molecular cloning, expression and regulatory activity of G alpha 11- and beta gamma-subunit-stimulated phospholipase C-beta from avian erythrocytes [1].
• Proteolytic modification of membrane-associated phospholipase C-beta by mu-calpain enhances its activation by G-protein beta gamma subunits in human platelets [23].
• PTH treatment of cells that express the NHERF2 PTH1R complex markedly activates phospholipase C beta and inhibits adenylyl cyclase through stimulation of inhibitory G proteins (G(i/o) proteins) [9].
• RGS4 and GAIP are GTPase-activating proteins for Gq alpha and block activation of phospholipase C beta by gamma-thio-GTP-Gq alpha [24].

Other interactions of PLCB1

• Overall, the results suggest that a ternary complex composed of LPA(2), NHERF2, and PLC-beta3 may play a key role in the LPA(2)-mediated PLC-beta signaling pathway [14].
• Together, these findings present a quantitative evaluation of the direct interactions between Rac GTPases and PLC-beta isozymes and define a novel role for the PH domain of PLC-beta2 as a putative effector site for Rac GTPases [25].
• A key step is the activation of phosphatidylinositol-specific phospholipase C (PI-PLC) within seconds following TcR/CD3 stimulation, an event which is strongly enhanced by co-ligation of the CD4 (or CD8) accessory molecule with TcR/CD3 [26].
• Phospholipase Cbeta and protein kinase C did not appear to significantly contribute to internalization of the TPbeta receptor, suggesting that Galpha(q) induces receptor internalization through a phospholipase Cbeta- and protein kinase C-independent pathway [27].
• The contents of PLC-beta1 and beta3 were not changed by the differentiation [28].

Analytical, diagnostic and therapeutic context of PLCB1

• Immunoprecipitation studies revealed that NHERF2 interacts specifically with PLC-beta3, but not with other PLC-beta isotypes [15].
• Size-exclusion chromatography data suggest that PLC-beta3 and PLC-beta1 form higher affinity homodimers than PLC-beta2 [16].
• We have also assigned by fluorescence in situ hybridization (FISH) analysis the PLC beta1 to human chromosome 20p12 [29].
• Murine NIH 3T3 fibroblasts were found to express PLC-gamma, but the expression of PLC-beta was barely detectable by radioimmunoassay or protein immunoblot [30].
• All of the eight PI-PLC isozymes examined in this study were found to be expressed to varying extents in the bovine parathyroid gland and in the CaR-transfected HEK cells as assessed by immunoblotting [31].

References