The regulation of phospholipase C-gamma 1 by phosphatidic acid. Assessment of kinetic parameters.

Jones, G A; Carpenter, Graham

doi:10.1016/s0021-9258(19)36862-0

Cited by 174 publications

(16 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although DGK activity terminates DAG signaling, it also creates PA (32,33,63). PA is a potent activator of PLCγ enzymatic activity in vitro (35). In addition, a recent report suggests that DGKζ, through production of PA, may increase intracellular PIP 2 by activation of PI5K Iα (37).…”

Section: Articlementioning

confidence: 99%

“…Additionally, PA itself is a second messenger, and DGK activity could regulate mast cell function by aff ecting PA accumulation. In vitro, PA is a potent activator of PLC and phosphatidylinositol 4-phosphate 5-kinase (PI5K), enzymes involved in PIP 2 degradation and production (35)(36)(37). Therefore, through conversion of DAG into PA, DGK enzymes could regulate many aspects of inositol lipid metabolism and mast cell activation after FcεRI engagement.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Impaired degranulation but enhanced cytokine production after FcεRI stimulation of diacylglycerol kinase ζ–deficient mast cells

Olenchock¹,

Guo²,

Silverman³

et al. 2006

The Journal of Cell Biology

View full text Add to dashboard Cite

Calcium and diacylglycerol are critical second messengers that together effect mast cell degranulation after allergen cross-linking of immunoglobulin (Ig)E-bound Fc RI. Diacylglycerol kinase (DGK) is a negative regulator of diacylglycerol-dependent signaling that acts by converting diacylglycerol to phosphatidic acid. We reported previously that DGK −/− mice have enhanced in vivo T cell function. Here, we demonstrate that these mice have diminished in vivo mast cell function, as revealed by impaired local anaphylactic responses. Concordantly, DGK −/− bone marrow-derived mast cells (BMMCs) demonstrate impaired degranulation after Fc RI cross-linking, associated with diminished phospholipase C activity, calcium fl ux, and protein kinase C-II membrane recruitment. In contrast, Ras-Erk signals and interleukin-6 production are enhanced, both during IgE sensitization and after antigen cross-linking of Fc RI. Our data demonstrate dissociation between cytokine production and degranulation in mast cells and reveal the importance of DGK activity during IgE sensitization for proper attenuation of Fc RI signals.

show abstract

Section: Articlementioning

confidence: 99%

mentioning

confidence: 99%

Impaired degranulation but enhanced cytokine production after FcεRI stimulation of diacylglycerol kinase ζ–deficient mast cells

Olenchock¹,

Guo²,

Silverman³

et al. 2006

The Journal of Cell Biology

View full text Add to dashboard Cite

show abstract

“…The PI-PLC isozymes, like many other enzymes involved in lipid signalling and metabolism, can reversibly associate with membranes. The binding to the membrane via sites on the enzyme distinct from the active site can be followed by multiple cycles of substrate hydrolysis [30][31][32][33]. This type of mechanism is known as 'processive' catalysis [34,35].…”

Section: Interaction Of Pi-plcs With the Membranementioning

confidence: 99%

Structural views of phosphoinositide-specific phospholipase C: signalling the way ahead

Williams

Katan²

1996

Structure

View full text Add to dashboard Cite

Recent structural studies of mammalian phosphoinositide-specific phospholipase C (PI-PLC) have begun to shed light on the mechanism whereby this family of effector enzymes is able to hydrolyze phospholipid substrates to yield second messengers. PI-PLC isozymes employ a variety of modules (PH domain, EF-hand domain, SH2 domain, SH3 domain and C2 domain) that are common in proteins involved in signal transduction to reversibly interact with membranes and protein components of the signalling pathways.

show abstract

“…Identification of different protein isoforrns was possible which is important since they may have different functions, cellular distributions or play a role at different stages of the process.Diacylglycerol kinases (DGK) of 4 different classes were identified by LARC, specifically DGK~l, 02, E, ~ and t. DGK is involved in production of PA from DAG, which together may function as second messengers modulating activity of enzymes such as PIP5K(Jenkins, Fisette et al 1994) and PKOyl(Jones and Carpenter 1993). DGK isoforrns contain different domains which alter their function and localization.…”

mentioning

confidence: 99%

Activated Fc receptor supramolecular complex

Petrenko¹

2021

Preprint

View full text Add to dashboard Cite

Phagocytosis is a part of immune response. IgG opsonized particles of greater than 1 um are recognized by Fcy receptors on the surface of professional phagocytes such as macrophages and neutrphils. IgGs are part of the immune system and is a cognate ligand of the Fc receptor. Live Cell Affinity Receptor chromatography (LARC) was used to capture an activated Fcy receptor supramolecular complex from the surface of live human neutrophils, by allowing IgG opsonized microbeads to bind to the cell surface. The cells were burst in PBS, collected and digested along side with controls. Isolated FcyR complex was analysed by LC-MS/MS. Fc and control experiment lists of SEQUEST correlated proteins were screened for a total cumulative score of at least 2400 and a minimum of three different peptides. This served as the basis of protein involvement in the FcyR mediated phagocytosis, which were then searched with iHOP for their interaction partners. Gathered interactions were then exported and Cytoscape, Osprey and String algorithms were used to generate network of interacting proteins. PAKs2-4 and PAK6 were detected with LARC. PAK2 and PAK4 were predicted by algorithms to have a central role in particle uptake. From Western Blotting, endogenous PAKs2-4 and PAK6 were detected in murine macrophages. Immunofluorescent staining was then used to verify the presence of these proteins in the forming phagosome and showed localization of PAKs to the phagosome. The same effect was observed with transfection of GFP constructs of PAKs. Upon transfection with dominant negative PAKs reduction in phagocytosis was observed.

show abstract

The regulation of phospholipase C-gamma 1 by phosphatidic acid. Assessment of kinetic parameters.

Cited by 174 publications

References 41 publications

Impaired degranulation but enhanced cytokine production after FcεRI stimulation of diacylglycerol kinase ζ–deficient mast cells

Impaired degranulation but enhanced cytokine production after FcεRI stimulation of diacylglycerol kinase ζ–deficient mast cells

Structural views of phosphoinositide-specific phospholipase C: signalling the way ahead

Activated Fc receptor supramolecular complex

Contact Info

Product

Resources

About