Phospholipase D2-generated phosphatidic acid couples EGFR stimulation to Ras activation by Sos

Zhao, Chen; Du, Guangwei; Skowronek, Karl; Frohman, Michael A.; Bar–Sagi, Dafna

doi:10.1038/ncb1594

Cited by 258 publications

(280 citation statements)

References 31 publications

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“…Upon EGF stimulation, SOS1 binds to phosphorylated EGFR through the adaptor protein GRB2, which then triggers RAS activation at the plasma membrane [40]. Interestingly, its GDP-GTP exchange activity, known to be crucial for EGF-dependent MAP kinases activation, is dispensable for NF-kB activation upon EGF stimulation, and this supports the notion that SOS1 may also act as a scaffold protein to transmit oncogenic signals [39].…”

Section: Reviewsupporting

confidence: 54%

EGFR and NF-κB: partners in cancer

Shostak

Chariot

2015

Trends in Molecular Medicine

184

158

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Section: Reviewsupporting

confidence: 54%

EGFR and NF-κB: partners in cancer

Shostak

Chariot

2015

Trends in Molecular Medicine

184

158

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“…PLD is a signaling enzyme that generates the second messenger PA implicated in many cellular processes like adhesion, integrin activation [28], cell spreading [29], chemotaxis [22] and Ras activation [30]. PA production by PLD is abrogated by primary alcohol derivates like ethanol or 1-butanol.…”

Section: Resultsmentioning

confidence: 99%

A novel role for phospholipase D as an endogenous negative regulator of platelet sensitivity

Elvers

Grenegård

Khoshjabinzadeh

et al. 2012

Cellular Signalling

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Platelet aggregation, secretion and thrombus formation play a critical role in primary hemostasis to prevent excessive blood loss. On the other hand, uncontrolled platelet activation leads to pathological thrombus formation resulting in myocardial infarction or stroke. Stimulation of heterotrimeric G-proteins by soluble agonists or immunoreceptor tyrosine based activation motif-coupled receptors that interact with immobilized ligands such as the collagen receptor glycoprotein (GP) VI lead to the activation of phospholipases that cleave membrane phospholipids to generate soluble second messengers. Platelets contain the phospholipase (PL) D1 and D2 which catalyze the hydrolysis of phosphatidylcholine to generate the second messenger phosphatidic acid (PA). The production of PA is abrogated by primary alcohols that have been widely used for the analysis of PLD-mediated processes.However, it is not clear if primary alcohols effectively reduce PA generation or if they induce PLD-independent cellular effects. In the present study we made use of the specific PLD inhibitor 5-fluoro-2-indolyl des-chlorohalopemide (FIPI) and show for the first time, that FIPI enhances platelet dense granule secretion and aggregation of human platelets. Further, FIPI has no effect on cytosolic Ca 2+ activity but needs proper Rho kinase signaling to mediate FIPI-induced effects on platelet activation. Upon FIPI treatment the phosphorylation of the PKC substrate pleckstrin was prominently enhanced suggesting that FIPI affects PKCmediated secretion and aggregation in platelets. Similar effects of FIPI were observed in platelets from mouse wild-type and Pld1 -/-mice pointing to a new role for PLD2 as negative regulator of platelet sensitivity.

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“…Thus, many BAR domains selectively associate with membranes of high curvature due to the shape of their concave surface and the greater ability for facilitating electrostatic interactions with the highly curved membranes. (18), and C2 domains (13). Recently, it was also demonstrated that lipid-binding domains could be regulated by pH.…”

Section: : S299-s304mentioning

confidence: 99%

Lipid binding domains: more than simple lipid effectors

Stahelin

2009

Journal of Lipid Research

123

104

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The spatial and temporal regulation of lipid molecules in cell membranes is a hallmark of cellular signaling and membrane trafficking events. Lipid-mediated targeting provides for strict control and versatility, because cell membranes harbor a large number of lipid molecules with variation in head group and acyl chain structures. Signaling and trafficking proteins contain a large number of modular domains that exhibit specific lipid binding properties and play a critical role in their localization and function. Nearly 20 years of research including structural, computational, biochemical and biophysical studies have demonstrated how these lipid-binding domains recognize their target lipid and achieve subcellular localization. The integration of this individual lipid-binding domain data in the context of the fulllength proteins, macromolecular signaling complexes, and the lipidome is only beginning to be unraveled and represents a target of therapeutic development. This review brings together recent findings and classical concepts to concisely summarize the lipid-binding domain field while illustrating where the field is headed and how the gaps may be filled in with new technologies.-Stahelin, R. V. Lipid binding domains: more than simple lipid effectors. J. Lipid Res. 2009. 50: S299-S304.

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Phospholipase D2-generated phosphatidic acid couples EGFR stimulation to Ras activation by Sos

Cited by 258 publications

References 31 publications

EGFR and NF-κB: partners in cancer

EGFR and NF-κB: partners in cancer

A novel role for phospholipase D as an endogenous negative regulator of platelet sensitivity

Lipid binding domains: more than simple lipid effectors

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