Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human monocytic cell line U937 possesses two classes of the IgG Fc receptor (Fc gamma R), a high-affinity 72-kDa Fc gamma R (Fc gamma RI) and a low-affinity 40-kDa Fc gamma R (Fc gamma RII). Cross-linking of either class of Fc gamma R in U937 cells elicits an increase in the concentration of free intracellular Ca2+. A rapid rise in the concentration of inositol 1,4,5-trisphosphate (Ins-1,4,5-P3) and of several other inositol phosphates derived from Ins-1,4,5-P3 was observed after cross-linking of Fc gamma Rs in U937 cells. This result suggests that Ins-1,4,5-P3, generated by the action of phospholipase C (PLC), acts as a second messenger by which Fc gamma Rs mobilize intracellular Ca2+ in U937 cells. The mechanism by which the cross-linking of Fc gamma Rs triggers activation of PLC was studied. Cross-linking of Fc gamma RI or Fc gamma RII resulted in a rapid and transient phosphorylation of PLC-gamma 1 on tyrosine residues. It has previously been shown that phosphorylation of PLC-gamma 1 on tyrosine residues activates its enzymatic activity in cells. Prior incubation of U937 cells with a protein tyrosine kinase inhibitor, herbimycin A, prevented the tyrosine phosphorylation of PLC-gamma 1 and the hydrolysis of phosphatidylinositol 4,5-bisphosphate induced by the cross-linking of Fc gamma Rs. Thus, Fc gamma RI and Fc gamma RII appear to be functionally coupled to a nonreceptor tyrosine kinase that phosphorylates PLC-gamma 1 after receptor cross-linking, thereby causing activation of PLC-gamma 1.
 ...
PMID:Tyrosine phosphorylation of phospholipase C-gamma 1 induced by cross-linking of the high-affinity or low-affinity Fc receptor for IgG in U937 cells. 137 7

The low affinity IgG Fc receptor, Fc gamma RIII, expressed on circulating neutrophils, natural killer (NK) cells, and tissue macrophages, is involved in effector functions such as cytotoxicity and immune complex clearance by these cells. While Fc gamma RIII is reported to be a phosphatidylinositol (PI)-linked, rather than peptide-linked, protein on neutrophils and NK cells, its membrane linkage in macrophages has not been studied. We examined the sensitivity of Fc gamma RIII to cleavage by PI-specific phospholipase C (PI-PLC) in cultured monocytes and alveolar tissue macrophages and report that this receptor is not PI-linked on these cells. We also observed normal levels of Fc gamma RIII on cultured monocytes of a patient with paroxysmal nocturnal hemoglobinuria, a disease in which PI-linked proteins are deficient. The results suggest that Fc gamma RIII occurs solely in a transmembrane form in cells of the monocyte/macrophage lineage. In addition, we studied Fc gamma RIII on a cloned NK cell line and found it to be resistant to the effects of PI-PLC under conditions that cleaved Fc gamma RIII on neutrophils. Taken together, our results provide evidence for a distinct form of Fc gamma RIII that differs from the neutrophil receptor in its structure and, possibly, in its function.
 ...
PMID:Monocyte/macrophage Fc gamma RIII, unlike Fc gamma RIII on neutrophils, is not a phosphatidylinositol-linked protein. 169 31

CD16 is an IgG Fc receptor that is predominantly expressed on human natural killer (NK) cells and granulocytes. The CD16 antigen expressed on neutrophils is a 50 to 70-kDa glycoprotein attached to the plasma membrane by a phosphatidylinositol-glycan linkage that is susceptible to cleavage by phosphatidylinositol-specific phospholipase C (PIPLC). By contrast, treatment of NK cells with PIPLC did not cleave CD16 from the cell surface. Biochemical analysis of the deglycosylated CD16 revealed a substantial difference in the core polypeptides expressed by NK cells and granulocytes. Culture of radiolabeled NK cells resulted in the spontaneous release of a CD16 molecule, smaller than the membrane form of CD16. These findings demonstrate that structural differences exist in the CD16 antigens expressed on NK cells and granulocytes that may potentially influence their functional activities.
 ...
PMID:Membrane anchoring and spontaneous release of CD16 (FcR III) by natural killer cells and granulocytes. 252

Recent evidence suggests a critical role for Syk in mast cell activation upon high affinity IgE receptor (FcepsilonRI) aggregation. A rat basophilic leukemia cell line, RBL-2H3, expresses similar levels of two Syk isoforms that differ with respect to the presence of a 23-amino acid insert within the "linker" region located between the second Src homology 2 and the catalytic domain. Although they exhibit comparable intrinsic enzymatic activity, functional differences between the two isoforms are unknown. Here we report that the deleted Syk isoform can mediate signal transduction in RBL-2H3 cells. Aggregation of chimeric kinase, consisting of either form of Syk fused to the transmembrane and extracellular domains of guinea pig type II IgG Fc receptor, on RBL transfectants resulted in degranulation, release of leukotrienes, and enhanced gene expression of tumor necrosis factor-alpha. The chimeras as well as phospholipase C-gamma1 and Vav became tyrosine-phosphorylated upon aggregation of chimeras. We also found that both Syk isoforms from transiently transfected COS-7 cells were capable of binding to phosphorylated FcepsilonRI, and their kinase activities were similarly up-regulated in the presence of tyrosine-phosphorylated synthetic peptides based on the sequence of the gamma subunit of FcepsilonRI. Thus, these results establish that both isoforms of Syk can mediate signal transduction in mast cells and suggest that the 23-amino acid insert in the linker region of Syk may not be obligatory for FcepsilonRI signaling.
 ...
PMID:Evidence for involvement of two isoforms of Syk protein-tyrosine kinase in signal transduction through the high affinity IgE receptor on rat basophilic leukemia cells. 960 11

PD-1 is an immunoreceptor that belongs to the immunoglobulin (Ig) superfamily and contains two tyrosine residues in the cytoplasmic region. Studies on PD-1-deficient mice have shown that PD-1 plays critical roles in establishment and/or maintenance of peripheral tolerance, but the mode of action is totally unknown. To study the molecular mechanism for negative regulation of lymphocytes through the PD-1 receptor, we generated chimeric molecules composed of the IgG Fc receptor type IIB (Fc gamma RIIB) extracellular region and the PD-1 cytoplasmic region and expressed them in a B lymphoma cell line, IIA1.6. Coligation of the cytoplasmic region of PD-1 with the B cell receptor (BCR) in IIA1.6 transformants inhibited BCR-mediated growth retardation, Ca(2+) mobilization, and tyrosine phosphorylation of effector molecules, including Ig beta, Syk, phospholipase C-gamma 2 (PLC gamma 2), and ERK1/2, whereas phosphorylation of Lyn and Dok was not affected. Mutagenesis studies indicated that these inhibitory effects do not require the N-terminal tyrosine in the immunoreceptor tyrosine-based inhibitory motif-like sequence, but do require the other tyrosine residue in the C-terminal tail. This tyrosine was phosphorylated and recruited src homology 2-domain-containing tyrosine phosphatase 2 (SHP-2) on coligation of PD-1 with BCR. These results show that PD-1 can inhibit BCR signaling by recruiting SHP-2 to its phosphotyrosine and dephosphorylating key signal transducers of BCR signaling.
 ...
PMID:PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine. 1169 46