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Gene Review

PLCB4  -  phospholipase C, beta 4

Homo sapiens

Synonyms: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4, ARCND2, PI-PLC, PLC-beta-4, Phosphoinositide phospholipase C-beta-4, ...
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Disease relevance of PLCB4

  • By using a retrovirus-derived system we generated derivatives of the human colon adenocarcinoma cell line LS174T (ATCC CL 188) that stably overexpress a full-length cDNA encoding the beta 1 isoform of bovine phosphoinositides-specific phospholipase C (PI-PLC) [1].
  • After a prolonged reperfusion time of 7 days after ischemia, both cytosolic and membrane-bound forms of PI-PLC were activated [2].
  • We conclude that the degradation of phosphatidylinositol by cytosolic phosphoinositide-phospholipase C may contribute to the pathophysiology of delayed neuronal death following cerebral ischemia [2].
  • Ischemia-reperfusion injury had no effect on Abeta-evoked alterations of synaptic plasma membrane-bound PI-PLC [2].
  • Phosphatidylinositol-specific phospholipase C (PIPLC) treatment of a B lymphoma cell line released 35% of the cell surface LFA-3 and 62% of DAF [3].

Psychiatry related information on PLCB4

  • The release of the neuraminidase by PI-PLC was dependent on the reaction time and the concentration of PI-PLC [4].

High impact information on PLCB4

  • Mammalian phosphoinositide-specific phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol [5].
  • The best characterized of the intranuclear lipids are the inositol lipids that form the components of a phosphoinositide-phospholipase C cycle [6].
  • The protein on NK cells has a molecular mass 6-10 kD larger than that on PMN, and, unlike the latter, is resistant to PI-specific phospholipase C (PI-PLC) [7].
  • However, when LFA-3 purified from human E was reconstituted in sheep E or human E and subjected to PIPLC treatment, 40-50% of LFA-3 was released from the cell membrane [3].
  • Treatment with PI-specific phospholipase C (PIPLC) releases 70-80, 60, and 10% of cell surface DAF from mononuclear cells, neutrophils, and erythrocytes, respectively [8].

Chemical compound and disease context of PLCB4

  • The X-ray crystal structure of the phosphatidylinositol-specific phospholipase C (PI-PLC) from the human pathogen Listeria monocytogenes has been determined both in free form at 2.0 A resolution, and in complex with the competitive inhibitor myo-inositol at 2.6 A resolution [9].
  • Quantitative solubilization of the phospholipid-associated form of acetylcholinesterase (AChE) from Torpedo electric organ can be achieved in the absence of detergent by treatment with phosphatidylinositol-specific phospholipase C (PIPLC) from Staphylococcus aureus [Futerman, Low & Silman (1983) Neurosci. Lett. 40, 85-89] [10].
  • A significant fraction of the amphiphilic AChE species was converted into hydrophilic components by incubation of the soluble enzyme with phosphatidylinositol-specific phospholipase C (PIPLC) from Bacillus thuringiensis, this fraction being increased by a double treatment with PIPLC and alkaline hydroxylamine [11].
  • In digitonin-permeabilized C6 glioma cells, the concentration-dependent increase of PI-PLC activation elicited by free Ca2+ was potentiated by the GTP analogue, guanosine 5'-[gamma-thio]triphosphate (GTP gamma S), with an EC50 of 6 microM [12].
  • This phosphonate inhibited the activity of phosphatidyl inositol-specific phospholipase C (PI-PLC) from Bacillus cereus with an IC50 of approximately 10 mM [13].

Biological context of PLCB4


Anatomical context of PLCB4

  • The stimulation of T cell receptor by cross-linked anti-CD3 mAb resulted in a rapid increase of the phosphatidylinositol-specific phospholipase C (PI-PLC) activity in whole cell lysates [18].
  • Tat, however, selectively stimulated a nuclear-specific PI-PLC with a peak of activity after 30 min from the addition in culture to Jurkat cells [18].
  • PI-PLC beta 1 overexpresser clones grew to form cell clumps floating in liquid medium, whereas the pMV7-introduced control clones displayed morphologic characteristics that were very similar to those of the parent LS174T cell line [1].
  • A combination of conventional and immunoaffinity chromatographic techniques was used to purify PIPLC beta 1 and beta 3 from rat brain membranes [19].
  • PIPLC beta 2 was purified from cytosol of HL60 cells [19].

Associations of PLCB4 with chemical compounds

  • cDNA sequence and gene locus of the human retinal phosphoinositide-specific phospholipase-C beta 4 (PLCB4) [20].
  • Phosphatidyl inositol-phospholipase C (PI-PLC) in squid retina was studied by immunoblotting and its activities were determined using [3H]phosphatidyl inositol bisphosphate ([3H]PIP2) as substrate [21].
  • GTP gamma S stimulated only the PI-PLC activity associated with membrane and was magnesium dependent [21].
  • A neurotoxic fragment of amyloid, Abeta 25-35, incubated in the presence of endogenous Ca2+, increased significantly the PI-PLC activity of normoxic brain [2].
  • These results provide evidence for a nonconserved role of this conserved alanine in coupling of group I GPCRs to PI PLC-activating G proteins and also suggest that this residue has differential roles in regulating expression and signaling by rat and human PAFRs [22].

Other interactions of PLCB4

  • 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 [23].
  • These results indicate that phospholipase C beta 4 is activated by G alpha subunits that are members of the Gq class, and, like the phospholipase C beta 1 isoform, it is refractory to activation in the transfection assay by many of the combinations of beta and gamma subunits found in the heterotrimeric G-proteins [14].

Analytical, diagnostic and therapeutic context of PLCB4

  • PI-PLC activity was determined by enzymatic assay, and protein expression of the PLC isozymes was determined by the Western blot technique [15].
  • Protein sequence analysis of a bovine brain phosphoinositide-specific phospholipase C (PI-PLC; PLC-154) has permitted the isolation of a cDNA that appears to code for this protein [24].
  • The availability of a highly specific probe moved us to perform in patients affected with MDS/AML, associated with normal karyotype, painting and fluorescence in situ hybridization (FISH) analysis aimed to check the inositide-specific phospholipase C (PI-PLC) beta1 gene, a player in the control of some checkpoints of the cell cycle [25].
  • The effective resolution of human platelet cytosolic phosphoinositide-phospholipase C (PLC) revealed five distinct activity peaks by Q-Sepharose and heparin-Sepharose column chromatographies when assayed using phosphatidylinositol (PI) and phosphatidylinositol 4,5-bisphosphate (PIP2) [26].
  • No role for glycosylphosphatidyl-inositol (GPI)-linked structures was demonstrated in these binding assays because the adhesion of leukemic blasts to stroma was not diminished after treatment with phosphatidylinositol-specific phospholipase C (PI-PLC) [27].


  1. Growth inhibition, enhancement of intercellular adhesion, and increased expression of carcinoembryonic antigen by overexpression of phosphoinositides-specific phospholipase C beta 1 in LS174T human colon adenocarcinoma cell line. Nomoto, K., Tomita, N., Miyake, M., Xhu, D.B., LoGerfo, P.R., Weinstein, I.B. Jpn. J. Cancer Res. (1998) [Pubmed]
  2. Alteration of phosphoinositide degradation by cytosolic and membrane-bound phospholipases after forebrain ischemia-reperfusion in gerbil: effects of amyloid beta peptide. Strosznajder, J., Zambrzycka, A., Kacprzak, M.D., Kopczuk, D., Strosznajder, R.P. Neurochem. Res. (1999) [Pubmed]
  3. Deficiency of lymphocyte function-associated antigen 3 (LFA-3) in paroxysmal nocturnal hemoglobinuria. Functional correlates and evidence for a phosphatidylinositol membrane anchor. Selvaraj, P., Dustin, M.L., Silber, R., Low, M.G., Springer, T.A. J. Exp. Med. (1987) [Pubmed]
  4. Phospholipase C-mediated release of neuraminidase from Tritrichomonas foetus cell surface. Dias Filho, B.P., De Souza, W., Andrade, A.F., Esteves, M.J., Angluster, J. Parasitol. Res. (1995) [Pubmed]
  5. Crystal structure of a mammalian phosphoinositide-specific phospholipase C delta. Essen, L.O., Perisic, O., Cheung, R., Katan, M., Williams, R.L. Nature (1996) [Pubmed]
  6. Nuclear lipid signalling. Irvine, R.F. Nat. Rev. Mol. Cell Biol. (2003) [Pubmed]
  7. Alternative membrane forms of Fc gamma RIII(CD16) on human natural killer cells and neutrophils. Cell type-specific expression of two genes that differ in single nucleotide substitutions. Ravetch, J.V., Perussia, B. J. Exp. Med. (1989) [Pubmed]
  8. Release of decay-accelerating factor (DAF) from the cell membrane by phosphatidylinositol-specific phospholipase C (PIPLC). Selective modification of a complement regulatory protein. Davitz, M.A., Low, M.G., Nussenzweig, V. J. Exp. Med. (1986) [Pubmed]
  9. Crystal structure of the phosphatidylinositol-specific phospholipase C from the human pathogen Listeria monocytogenes. Moser, J., Gerstel, B., Meyer, J.E., Chakraborty, T., Wehland, J., Heinz, D.W. J. Mol. Biol. (1997) [Pubmed]
  10. Physicochemical behaviour and structural characteristics of membrane-bound acetylcholinesterase from Torpedo electric organ. Effect of phosphatidylinositol-specific phospholipase C. Futerman, A.H., Fiorini, R.M., Roth, E., Low, M.G., Silman, I. Biochem. J. (1985) [Pubmed]
  11. Monomers and dimers of acetylcholinesterase in human meningioma are anchored to the membrane by glycosylphosphatidylinositol. Sáez-Valero, J., Vidal, C.J. Neurosci. Lett. (1995) [Pubmed]
  12. Potentiation of stimulus-induced phosphoinositide breakdown by calmodulin antagonists in C6 glioma cells. Lin, W.W. Naunyn Schmiedebergs Arch. Pharmacol. (1995) [Pubmed]
  13. Preparation and application of an affinity matrix for phosphatidylinositol-specific phospholipase C. Shashidhar, M.S., Keana, J.F., Volwerk, J.J., Griffith, O.H. Chem. Phys. Lipids (1990) [Pubmed]
  14. Activation of phospholipase C beta 4 by heterotrimeric GTP-binding proteins. Jiang, H., Wu, D., Simon, M.I. J. Biol. Chem. (1994) [Pubmed]
  15. Low phosphoinositide-specific phospholipase C activity and expression of phospholipase C beta1 protein in the prefrontal cortex of teenage suicide subjects. Pandey, G.N., Dwivedi, Y., Pandey, S.C., Teas, S.S., Conley, R.R., Roberts, R.C., Tamminga, C.A. The American journal of psychiatry. (1999) [Pubmed]
  16. Contrasting effects of phosphatidylinositol- and phosphatidylcholine-specific phospholipase C on apoptosis in cultured endothelial cells. Liu, X., Zhao, Q., Araki, S., Zhang, S., Miao, J. Endothelium (2006) [Pubmed]
  17. Cloning of cDNA encoding rat phospholipase C-beta 4, a new member of the phospholipase C. Kim, M.J., Bahk, Y.Y., Min, D.S., Lee, S.J., Ryu, S.H., Suh, P.G. Biochem. Biophys. Res. Commun. (1993) [Pubmed]
  18. Exogenous human immunodeficiency virus type-1 Tat protein selectively stimulates a phosphatidylinositol-specific phospholipase C nuclear pathway in the Jurkat T cell line. Zauli, G., Previati, M., Caramelli, E., Bassini, A., Falcieri, E., Gibellini, D., Bertolaso, L., Bosco, D., Robuffo, I., Capitani, S. Eur. J. Immunol. (1995) [Pubmed]
  19. Regulation of purified subtypes of phosphatidylinositol-specific phospholipase C beta by G protein alpha and beta gamma subunits. Smrcka, A.V., Sternweis, P.C. J. Biol. Chem. (1993) [Pubmed]
  20. cDNA sequence and gene locus of the human retinal phosphoinositide-specific phospholipase-C beta 4 (PLCB4). Alvarez, R.A., Ghalayini, A.J., Xu, P., Hardcastle, A., Bhattacharya, S., Rao, P.N., Pettenati, M.J., Anderson, R.E., Baehr, W. Genomics (1995) [Pubmed]
  21. Phosphatidyl inositol-phospholipase C in squid photoreceptor membrane is activated by stable metarhodopsin via GTP-binding protein, Gq. Suzuki, T., Narita, K., Yoshihara, K., Nagai, K., Kito, Y. Vision Res. (1995) [Pubmed]
  22. Lack of constitutive activation or inactivation of the platelet-activating factor receptor by glutamate substitution of alanine 230. Carlson, S.A., Chatterjee, T.K., Fisher, R.A. Receptors & signal transduction. (1996) [Pubmed]
  23. Decreased expression of phospholipase C-beta 2 isozyme in human platelets with impaired function. Lee, S.B., Rao, A.K., Lee, K.H., Yang, X., Bae, Y.S., Rhee, S.G. Blood (1996) [Pubmed]
  24. Determination of the primary structure of PLC-154 demonstrates diversity of phosphoinositide-specific phospholipase C activities. Katan, M., Kriz, R.W., Totty, N., Philp, R., Meldrum, E., Aldape, R.A., Knopf, J.L., Parker, P.J. Cell (1988) [Pubmed]
  25. Inositide-specific phospholipase c beta1 gene deletion in the progression of myelodysplastic syndrome to acute myeloid leukemia. Lo Vasco, V.R., Calabrese, G., Manzoli, L., Palka, G., Spadano, A., Morizio, E., Guanciali-Franchi, P., Fantasia, D., Cocco, L. Leukemia (2004) [Pubmed]
  26. Effects of gelsolin on human platelet cytosolic phosphoinositide-phospholipase C isozymes. Banno, Y., Nakashima, T., Kumada, T., Ebisawa, K., Nonomura, Y., Nozawa, Y. J. Biol. Chem. (1992) [Pubmed]
  27. Expression of integrins and examination of their adhesive function in normal and leukemic hematopoietic cells. Liesveld, J.L., Winslow, J.M., Frediani, K.E., Ryan, D.H., Abboud, C.N. Blood (1993) [Pubmed]
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