Disease relevance of Plcd1

• Two amino acids in the PLC-delta 1 PH domain that contact Ins(1,4,5)P3 have counterparts in the Bruton's tyrosine kinase (Btk) PH domain, where mutational changes cause inherited agammaglobulinemia, suggesting a mechanism for loss of function in Btk mutants [1].
• These results suggest that PLC-delta 1 would play an important role in the development of hypertension [2].
• We expressed rat PLC-delta 1 in Escherichia coli as a fusion protein with glutathione S-transferase, and found that the bacterial lysate shows a significant amount of Ins(1,4,5)P3 binding [3].
• Recombinant PLC-delta 4 was purified from extracts of HeLa cells that had been infected with vaccinia virus containing the corresponding cDNA [4].
• We examined the expression of an isozyme of PLC, PLC-delta, in rat colon neoplasms induced by methylazoxymethanol (MAM) acetate [5].

Psychiatry related information on Plcd1

• Western blot analysis using a specific antibody for PLC-delta showed that the concentration of PLC-delta protein was significantly higher in the cytosolic fraction of Alzheimer disease cortical tissue than in control brains [6].

High impact information on Plcd1

• Crystal structure of a mammalian phosphoinositide-specific phospholipase C delta [7].
• Western blot analysis revealed that in renal cortical membranes, fenoldopam and pramipexole increased expression of PLC beta 1 and decreased expression of PLC gamma 1; PLC delta was unchanged [8].
• This novel p122-RhoGAP binds to PLC-delta 1 and activates the phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolyzing activity of PLC-delta 1 [9].
• C2 domain conformational changes in phospholipase C-delta 1 [10].
• We report herein that the isolated PH domain from PLC-delta 1 binds to both PtdIns(4,5)P2 and Ins(1,4,5)P3 with high affinity and shows the same binding specificity seen by others with whole PLC-delta 1 [11].

Biological context of Plcd1

• Assignment of the rat phospholipase C-delta1 gene (Plcd1) to rat chromosome band 8q32 by fluorescence in situ hybridization and radiation hybrid mapping [12].
• A new phospholipase C delta 4 is induced at S-phase of the cell cycle and appears in the nucleus [13].
• Nuclear PLC delta 4 dramatically increases at the transition from G1- to S-phase, and the high content continues to the end of M-phase [13].
• These results suggest that PLC delta 4 is expressed in nucleus in response to mitogenic stimulation and plays important roles in cell growth as one of the early genes expressed during the transition from G1- to S-phase in the cell cycle [13].
• PLC delta 4 almost disappears when cells re-enter the next G1-phase [13].

Anatomical context of Plcd1

• PC12 cells contain at least three immunologically distinct phospholipase C (PLC) isozymes, PLC-beta, PLC-gamma, and PLC-delta [14].
• Phospholipase C delta 1 was detected in rat tail artery, mesenteric artery, aorta, and brain [15].
• These three regions were further evaluated with full-length TGIIs by constructing and coexpressing each site-directed mutant with the alpha 1B-AR and PLC-delta 1 in COS-1 cells [16].
• PLC delta 1 immunoreactivity was found in the glands and in the perinuclear region and dendrites of some receptor neurons [17].
• To determine directly if fuels activate these PLC isozymes, clones stably overexpressing PLC beta 1 or PLC delta 1 were generated in the fuel-sensitive beta cell line RINm5F, and secretagogue regulation of these PLC isoforms was determined [18].

Associations of Plcd1 with chemical compounds

• Ins(1,4,5)P3 at concentrations greater than 1 microM strongly inhibited 85-kDa phospholipase C delta activity, without changing its dependence on the concentrations of free Ca2+ and H+ [19].
• Treatment of C6Bu1 cells with cAMP-elevating agents (cholera toxin, isobutylmethylxanthine, forskolin, and 8-bromo-cAMP) increased serine phosphate in PLC-gamma, but the phosphate contents in PLC-beta and PLC-delta were not changed [20].
• While the levels of PLC-delta, another detectable PLC isozyme, were not altered by genistein suggesting that tyrosine kinase plays an important role in the association of PLC-gamma 1 with membranes [21].
• Interestingly, [Arg(8)] vasopressin-stimulated, but not carbachol-stimulated, IP accumulation was significantly increased in clones overexpressing either PLC beta 1 or PLC delta 1 [18].
• In contrast, overexpression of PLC delta 1 had no effect on glyceraldehyde- or AlF(4)(-)-stimulated IP accumulation [18].

Other interactions of Plcd1

• A dual functional signal mediator showing RhoGAP and phospholipase C-delta stimulating activities [9].
• On the other hand, the contents of PLC beta 1, PLC gamma 1, and PLC delta 1 do not change significantly during the cell cycle [13].
• In cultured VSMC, PLC-gamma 1 and PLC-delta 1 isozymes, but not PLC-beta 1, were identified by Western analysis [22].
• Modulation of intracellular Ca(2+) via alpha(1B)-adrenoreceptor signaling molecules, G alpha(h) (transglutaminase II) and phospholipase C-delta 1 [23].
• Plasma membrane phosphatidylinositol 4,5-bisphosphate pools were increased upon NCS-1 transfection as visualized using a phospholipase C-delta pleckstrin homology domain-green fluorescent protein construct [24].

Analytical, diagnostic and therapeutic context of Plcd1

• Western blot analysis and immunocytochemical staining showed that PLC delta 4 is dominantly present in nucleus [13].
• Immunofluorescence techniques were used to investigate the subcellular localization of two PLC isozymes (PLC-gamma and PLC-delta) in normal and simian virus 40-transformed REF52 cells to determine (i) if PLC colocalizes with alpha-PKC and (ii) if PLC isozyme distribution is sensitive to transformation [25].
• In this study, interaction sites on TGII for the alpha 1B-AR were identified using a peptide approach and site-directed mutagenesis, including in vivo reconstitution of TGIIs with the alpha 1B-AR and PLC-delta 1 [16].
• Expression of PLC-delta in the neoplasms was not detected by northern blot analysis, and a low level of expression was detected by immunoblot analysis, although PLC-delta expression was apparent in the non-neoplastic colon mucosae of MAM acetate-treated rats as well as in the colon mucosae of control rats [5].
• Expression, characterization, and crystallization of the catalytic core of rat phosphatidylinositide-specific phospholipase C delta 1 [26].

References