Phospholipase Cγ activation and phosphoinositide hydrolysis are essential for embryonal development

Schlessinger, Joseph

doi:10.1073/pnas.94.7.2798

Cited by 14 publications

(9 citation statements)

References 21 publications

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“…Of all the known PLC isozymes, PLC7 (y~and Y2) are the only isozymes that have been shown in nonocular tissues to be activated by phosphorylation by either receptor or nonreceptor tyrosine kinases (for reviews, see Rhee, 1992;Schlessinger, 1997). The observed specific effect of ATP and not GTP (data not shown) on PLC activity in this study may be indicative of phosphorylation of PLC71 or, alternatively, suggest the phosphorylation of another protein that might regu- late PLC activity.…”

Section: Discussionmentioning

confidence: 60%

Phospholipase Cγ₁ in Bovine Rod Outer Segments: Immunolocalization and Light‐Dependent Binding to Membranes

Ghalayini¹,

Weber²,

Rundle

et al. 1998

Journal of Neurochemistry

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We have investigated the isozymes of a phosphoinositide‐specific phospholipase C (PLC) in bovine retina using several monoclonal antisera to PLCβ1, γ1, and δ1. Immunoblot analysis showed that all three isozymes were present in the retina. Immunocytochemical localization in frozen bovine retina sections showed that PLCγ1 was present in the photoreceptor cell layer, outer plexiform cell layer, inner plexiform cell layer, and ganglion cell layer. Immunoreaction within the photoreceptor cell layer was dependent on dark/light adaptation state of retinas. Immunoblot analysis of rod outer segments (ROS) with monoclonal or polyclonal antibodies to PLCγ1 showed the presence of an immunoreactive band of 140 kDa. ROS prepared from retinas light‐adapted in vitro had more PLCγ1 on immunoblots than ROS from dark‐adapted retinas. PLC enzyme activity in ROS from light‐adapted retinas was 69 and 46% higher than ROS from dark‐adapted retinas, when assayed in the presence and absence of ATP, respectively. This increase in enzyme activity was observed at [Ca2+]free between 0.32 and 100 µM. These results demonstrate the presence of PLCγ1 in bovine ROS and show that ROS prepared from light‐adapted retinas are enriched in this isozyme, suggesting that light may promote the binding of this isozyme to bleached ROS membranes.

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Section: Discussionmentioning

confidence: 60%

Phospholipase Cγ₁ in Bovine Rod Outer Segments: Immunolocalization and Light‐Dependent Binding to Membranes

Ghalayini¹,

Weber²,

Rundle

et al. 1998

Journal of Neurochemistry

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“…For example, phosphorylation of a conserved tyrosine in the C-terminal tail of FGFRs creates a docking site for Phospholipase Cγ1 (PLCγ1), a tandem SH2-containing substrate (Eswarakumar et al, 2005; Mohammadi et al, 1991; Peters et al, 1992). This recruitment plays a dual role in the activation of the PLCγ pathway: 1) it facilitates phosphorylation of PLCγ which relieves PLCγ autoinhibition, resulting in upregulation of the lipase activity of the enzyme (Bunney et al, 2012b; Hajicek et al, 2013; Poulin et al, 2005), 2) it translocates PLCγ to the vicinity of its substrate phosphatidylinositol 4,5-bisphosphate (PIP2) in the plasma membrane, where the activated enzyme can hydrolyze PIP2 leading to the generation of the second messengers DAG and IP3 (Ellis et al, 1998; Schlessinger, 1997). …”

Section: Introductionmentioning

confidence: 99%

Two FGF Receptor Kinase Molecules Act in Concert to Recruit and Transphosphorylate Phospholipase Cγ

et al. 2016

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SUMMARY The molecular basis by which receptor tyrosine kinases (RTKs) recruit and phosphorylate Src Homology 2 (SH2) domain-containing substrates has remained elusive. We used X-ray crystallography, NMR spectroscopy, and cell-based assays to demonstrate that recruitment and phosphorylation of Phospholipase Cγ (PLCγ), a prototypical SH2 containing substrate, by FGF receptors (FGFR) entails formation of an allosteric 2:1 FGFR-PLCγ complex. We show that the engagement of pTyr-binding pocket of the cSH2 domain of PLCγ by the phosphorylated tail of an FGFR kinase induces a conformational change at the region past the cSH2 core domain encompassing Tyr-771 and Tyr-783 to facilitate the binding/phosphorylation of these tyrosines by another FGFR kinase in trans. Our data overturn the current paradigm that recruitment and phosphorylation of substrates are carried out by the same RTK monomer in cis, and disclose an obligatory role for receptor dimerization in substrate phosphorylation in addition to its canonical role in kinase activation.

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“…The PLC␥1 isoform is ubiquitously expressed, whereas PLC␥2 is predominantly expressed in hemopoietic cells (39). The potential physiological role of PLC␥1 has been approached by the derivation of mice that lack the enzyme.…”

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confidence: 99%

Phospholipase Cγ2 Is Essential for Specific Functions of FcεR and FcγR

Wen

Jou

Chen

et al. 2002

The Journal of Immunology

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Phospholipase Cγ2 (PLCγ2) plays a critical role in the functions of the B cell receptor in B cells and of the FcRγ chain-containing collagen receptor in platelets. Here we report that PLCγ2 is also expressed in mast cells and monocytes/macrophages and is activated by cross-linking of FcεR and FcγR. Although PLCγ2-deficient mice have normal development and numbers of mast cells and monocytes/macrophages, we demonstrate that PLCγ2 is essential for specific functions of FcεR and FcγR. While PLCγ2-deficient mast cells have normal mitogen-activated protein kinase activation and cytokine production at mRNA levels, the mutant cells have impaired FcεR-mediated Ca2+ flux and inositol 1,4,5-trisphosphate production, degranulation, and cytokine secretion. As a physiological consequence of the effect of PLCγ2 deficiency, the mutant mice are resistant to IgE-mediated cutaneous inflammatory skin reaction. Macrophages from PLCγ2-deficient mice have no detectable FcγR-mediated Ca2+ flux; however, the mutant cells have normal FcγR-mediated phagocytosis. Moreover, PLCγ2 plays a nonredundant role in FcγR-mediated inflammatory skin reaction.

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Phospholipase Cγ activation and phosphoinositide hydrolysis are essential for embryonal development

Cited by 14 publications

References 21 publications

Phospholipase Cγ₁ in Bovine Rod Outer Segments: Immunolocalization and Light‐Dependent Binding to Membranes

Phospholipase Cγ₁ in Bovine Rod Outer Segments: Immunolocalization and Light‐Dependent Binding to Membranes

Two FGF Receptor Kinase Molecules Act in Concert to Recruit and Transphosphorylate Phospholipase Cγ

Phospholipase Cγ2 Is Essential for Specific Functions of FcεR and FcγR

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Phospholipase Cγ activation and phosphoinositide hydrolysis are essential for embryonal development

Cited by 14 publications

References 21 publications

Phospholipase Cγ1 in Bovine Rod Outer Segments: Immunolocalization and Light‐Dependent Binding to Membranes

Phospholipase Cγ1 in Bovine Rod Outer Segments: Immunolocalization and Light‐Dependent Binding to Membranes

Two FGF Receptor Kinase Molecules Act in Concert to Recruit and Transphosphorylate Phospholipase Cγ

Phospholipase Cγ2 Is Essential for Specific Functions of FcεR and FcγR

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Phospholipase Cγ₁ in Bovine Rod Outer Segments: Immunolocalization and Light‐Dependent Binding to Membranes

Phospholipase Cγ₁ in Bovine Rod Outer Segments: Immunolocalization and Light‐Dependent Binding to Membranes