Disease relevance of PLCB2

• 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 [1].
• Activation of PLC-beta 2 by beta gamma subunits may be an important mechanism by which pertussis toxin-sensitive G proteins stimulate PLC [2].
• Mechanosensitivity of human osteosarcoma cells and phospholipase C beta2 expression [3].
• Immunoblotting analysis revealed that human astrocytoma cells expressed phospholipase C (PLC)-beta1 and -beta3, but not PLC-beta2 [4].
• PLC-beta2 is highly expressed in breast cancer and is associated with a poor outcome: a study on tissue microarrays [5].

High impact information on PLCB2

• Furthermore, we show that PKA directly phosphorylates serine residues of the PLC-beta 2 protein both in vivo and in vitro [6].
• We report here that PLC-beta 1 and PLC-beta 2 were stimulated by free beta gamma subunits and that PLC-beta 2 was the most sensitive to beta gamma stimulation [2].
• Isozyme-selective stimulation of phospholipase C-beta 2 by G protein beta gamma-subunits [2].
• Analysis of the ability of these mutants to regulate the activity of calcium and potassium channels, adenylyl cyclase 2, phospholipase C-beta2, and beta-adrenergic receptor kinase revealed the Gbeta residues required for activation of each effector and provides evidence for partially overlapping domains on Gbeta for regulation of these effectors [7].
• The best characterized of the intranuclear lipids are the inositol lipids that form the components of a phosphoinositide-phospholipase C cycle [8].

Chemical compound and disease context of PLCB2

• In order to investigate whether mastoparan stimulate PLC via pertussis toxin-insensitive alpha q, a deletion mutant of PLC beta 2 deficient of the site of interaction with alpha q-subunits was expressed in COS-1 cells [9].

Biological context of PLCB2

• Also, the peptide was able to inhibit PI(4,5)P2 and G beta gamma activation of the PH-PLC delta 1 PH-PLC beta 2 enzymes in a concentration-dependent manner, suggesting that this is the region responsible for PH domain-mediated activation of the catalytic core [10].
• Selective up-regulation of phospholipase C-beta2 during granulocytic differentiation of normal and leukemic hematopoietic progenitors [11].
• Assignment1 of human PLCB2 encoding PLC beta2 to human chromosome 15q15 by fluorescence in situ hybridization [12].
• We identified the N-terminal segment of PLC beta 2 with amino acid sequence extending to the end of the Y box as the region required for activation by G beta gamma and the C-terminal region as the segment containing amino acid sequences required for activation by G alpha [13].
• Overexpression of phospholipase C-beta2 led to increased hCG-stimulated inositol phosphate accumulation, and expression of a beta-ARK1 C-terminal polypeptide effectively suppressed hCG-mediated phosphatidylinositol hydrolysis [14].

Anatomical context of PLCB2

• Using the yeast two-hybrid technique to screen a leukocyte library we identified mitogen-activated protein kinase kinase 3 (MKK3) as a partner of PLC-beta 2 [15].
• Taken together, these data show that PLC-beta2 represents a sensitive and reliable marker of neutrophil maturation of normal and malignant myeloid progenitors [11].
• Remarkably, using primary blasts purified from bone marrow of patients affected by APL successfully induced to remission by treatment with ATRA, we showed a striking correlation between the amount of PLC-beta2 expression and the responsiveness of APL blasts to the differentiative activity of ATRA [11].
• We found the sequence extending from residue Glu-435 to residue Val-641 inhibited Gbeta-gamma-mediated activation of PLC beta2 in transfected COS-7 cells [16].
• PLD and PI-PLC activities in these four transfected cell lines as well as in nontransfected cells were measured by the formation of [3H]phosphatidylethanol [( 3H]PEt) and [3H]inositol phosphates [( 3H]IP) after labeling cellular phospholipids with [3H]oleic acid and [3H]inositol [17].

Associations of PLCB2 with chemical compounds

• Mammalian inositol-specific phospholipase C-beta2 (PLC beta 2) and PLC delta 1 differ in their cellular activators [10].
• PLC beta 2 can be activated by G beta gamma subunits, whereas PLC delta 1 can be activated by phosphatidylinositol 4,5 bisphosphate (PI(4,5)P2) [10].
• Phospholipase C (PLC)-beta1 and PLC-beta2 are regulated by the Gq family of heterotrimeric G proteins and contain C2 domains [18].
• In addition, the Ggamma2 and Ggamma3 mutants with substitution of the C-terminal Cys residue by a Ser residue, which can inhibit wild type Gbetagamma-mediated activation of PLC beta2, were able to inhibit C5a or fMLP-mediated activation of PLC beta2 [19].
• Thus, PLC beta 1 activity increased 7-fold and PLC beta 2 activity increased 4-fold when the mol % of PIP2 in the monolayer increased from 17.9% to 29%, increasing further thereafter [20].

Physical interactions of PLCB2

• Phospholipase C-beta 2 interacts with mitogen-activated protein kinase kinase 3 [15].
• Identification of a structural element in phospholipase C beta2 that interacts with G protein betagamma subunits [21].

Regulatory relationships of PLCB2

• An increase of PLC-beta2 expression also characterized the cytokine-induced granulocytic differentiation of CD34+ normal hematopoietic progenitors [11].
• Furthermore, we found that coexpression of G alpha 16 and G beta 1 gamma 1 but not G beta 1 gamma 5 in COS-7 cells was able to synergistically activate recombinant PLC beta 2 [13].
• In contrast, G alpha 11 promoted only a small elevation in the catalytic rate of recombinant PLC-beta 2, which was also typical of the native isoenzyme [22].
• Phospholipase C beta2 (PLC beta2) is activated by G protein betagamma subunits and calcium [23].
• In previous work (Sankaran, B., Osterhout, J., Wu, D., and Smrcka, A. V. (1998) J. Biol. Chem. 273, 7148-7154), we showed that overlapping peptides, N20K (Asn(564)-Lys(583)) and E20K (Glu(574)-Lys(593)), from the catalytic domain of phospholipase C (PLC) beta2 block Gbetagamma-dependent activation of PLC beta2 [24].

Other interactions of PLCB2

• 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].
• Case-control analyses revealed modest evidence (0.01 < P < 0.05) for association between a single variant in PLCB2 and two variants in PLA2G4B [26].
• Compared with normal platelets, platelets from the patient contained approximately one-third the amount of PLC-beta 2, whereas PLC-beta 4 was increased threefold [27].
• These results suggest that the impaired platelet function in the patient in response to multiple G protein mediated agonists is attributable to a deficiency of PLC-beta 2 [27].
• The pleckstrin homology domain of phospholipase C-beta2 as an effector site for Rac [25].

Analytical, diagnostic and therapeutic context of PLCB2

• The interaction was confirmed by co-immunoprecipitation assays which indicated that MKK3 interacts with PLC-beta 2, but not with other PLC-betas [15].
• Size-exclusion chromatography data suggest that PLC-beta3 and PLC-beta1 form higher affinity homodimers than PLC-beta2 [28].
• This protein was coupled to a pertussis toxin (PTX)-sensitive Gbeta1 subunit whose transducer was PLC-beta2, which triggered a rapid (5 sec) mobilization of calcium from the endoplasmic reticulum [29].
• By immunoblotting, eosinophil PLC-beta2 and -gamma2 isoforms were identified, and PLC activation was measured as a function of inositol 1,4,5-trisphosphate concentration [30].
• To examine the structure-function relationships of a PLC beta isozyme highly sensitive to beta gamma subunit stimulation, we have altered the cDNA of PLC beta 2 by site-directed mutagenesis and have examined the effects of these structural alterations on the functional properties of the mutant polypeptides [31].

References