Interaction of Elongation Factor-1α and Pleckstrin Homology Domain of Phospholipase C-γ1 with Activating Its Activity

Chang, Jen-Yuan; Seok, Heon; Kwon, Taeg Kyu; Min, Do Sik; Ahn, Bong Hyun; Lee, Young Han; Suh, Ju Won; Kim, Jong Woo; Iwashita, Shintaro; Omori, Akira; Ichinose, Sachiyo; Numata, Osamu; Seo, Jeong Kon; Oh, Yong‐Seok; Suh, Pann Ghill

doi:10.1074/jbc.m111206200

Cited by 46 publications

(47 citation statements)

References 45 publications

(32 reference statements)

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“…Indeed, EF-1␣ has been shown to bind and modulate activities of diverse signaling proteins such as calmodulin (77), PLC-␥1 (78) and was shown to interact with muscarinic acetylcholine receptors (79). The role of EF-1␣ in the PSD has not been examined.…”

Section: Discussionmentioning

confidence: 99%

Proteomics Analysis of Rat Brain Postsynaptic Density

Hornshaw

Schors

et al. 2004

Journal of Biological Chemistry

235

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The postsynaptic density contains multiple protein complexes that together relay the presynaptic neurotransmitter input to the activation of the postsynaptic neuron. In the present study we took two independent proteome approaches for the characterization of the protein complement of the postsynaptic density, namely 1) two-dimensional gel electrophoresis separation of proteins in conjunction with mass spectrometry to identify the tryptic peptides of the protein spots and 2) isolation of the trypsin-digested sample that was labeled with isotope-coded affinity tag, followed by liquid chromatography-tandem mass spectrometry for the partial separation and identification of the peptides, respectively. Functional grouping of the identified proteins indicates that the postsynaptic density is a structurally and functionally complex organelle that may be involved in a broad range of synaptic activities. These proteins include the receptors and ion channels for glutamate neurotransmission, proteins for maintenance and modulation of synaptic architecture, sorting and trafficking of membrane proteins, generation of anaerobic energy, scaffolding and signaling, local protein synthesis, and correct protein folding and breakdown of synaptic proteins. Together, these results imply that the postsynaptic density may have the ability to function (semi-) autonomously and may direct various cellular functions in order to integrate synaptic physiology.The majority of excitatory neurotransmission in the brain occurs via glutamatergic synapses. In the presynaptic element of the synapse, specialized secretion machinery determines the activity-dependent membrane fusion of glutamate-containing vesicles and the release of transmitter into the synaptic cleft. In the postsynaptic element, glutamate receptors and downstream signal transduction are organized by the protein assembly of the postsynaptic density (PSD). 1 Both the presynaptic release machinery and the PSD are electron-dense assemblies (1, 2), in which proteins are thought to be organized into distinct functional complexes (3-5) that may be dynamically regulated by neuronal activity (6 -8). The modulation of this molecular architecture of the synapse is at the basis of synaptic plasticity (6 -8), and aberrations thereof may underlie neuronal disorders.In view of the importance of the PSD in glutamatergic neurotransmission and its involvement in neuroplasticity, considerable efforts have been made to identify its protein constituents as a prelude to understand the molecular basis of PSD functioning. In the past several years, yeast two-hybrid technology has been extensively used to characterize proteins that interact with the glutamate receptors and may constitute core elements of the PSD involved in the regulation of receptor trafficking and signaling (reviewed in Refs. 9 -11). Based largely on these studies a protein-protein interaction map of the PSD has emerged. In brief, the model posits that the postsynaptic receptor complexes are localized by scaffolding proteins such as the s...

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Section: Discussionmentioning

confidence: 99%

Proteomics Analysis of Rat Brain Postsynaptic Density

Hornshaw

Schors

et al. 2004

Journal of Biological Chemistry

235

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“…Tyrosine 509 and phenylalanine 510 in the sPHN domain regulate SH2C domain activity. PH⌬ PLC-␥1 constructs are not functional because the deleted sPHN domain contains the binding site for the substrate PI(4,5)P 2 (3,18). In an effort to maintain PI(4,5)P 2 binding while disrupting sPHN-mediated regulation of the SH2C domain, a series of site-specific PLC-␥1 mutations were made and screened in the pY132 LAT ELISA for SH2N domain-independent binding activity.…”

Section: Vol 27 2007 Intramolecular Regulation Of Phospholipase C-␥mentioning

confidence: 99%

“…Because phenylalanine is structurally similar to tyrosine, the tyrosine-to-phenylalanine mutants may not have altered sPHN domain interactions sufficiently. Therefore, a second series of mutants, based on those of Chang et al (3), were constructed in which various amino acids, including some of the tyrosine residues, were replaced with alanine. None of the sPHN mutations of PLC-␥1 prevented interaction with pY132 LAT, and while in some experiments the mutants demonstrated greater binding to pY132 LAT than WT PLC-␥1, this was not a consistent finding (data not shown).…”

Section: Vol 27 2007 Intramolecular Regulation Of Phospholipase C-␥mentioning

confidence: 99%

“…PLC-␥1 hydrolyzes phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ], leading to the generation of the second messengers, inositol triphosphate (IP 3 ) and diacylglycerol, which release Ca 2ϩ from intracellular stores and activate Ras through the RasGRP/protein kinase C pathway, respectively (8,13). PLC-␥1 has also been shown to play a role in the activation of NF-B (7).…”

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confidence: 99%

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Intramolecular Regulation of Phospholipase C-γ1 by Its C-Terminal Src Homology 2 Domain

DeBell

Graham

Reischl

et al. 2007

Molecular and Cellular Biology

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Phosphoinositide-specific phospholipase C-␥1 (PLC-␥1) is a key enzyme that governs cellular functions such as gene transcription, secretion, proliferation, motility, and development. Here, we show that PLC-␥1 is regulated via a novel autoinhibitory mechanism involving its carboxy-terminal Src homology (SH2C) domain. Mutation of the SH2C domain tyrosine binding site led to constitutive PLC-␥1 activation. The amino-terminal split pleckstrin homology (sPHN) domain was found to regulate the accessibility of the SH2C domain. PLC-␥1 constructs with mutations in tyrosine 509 and phenylalanine 510 in the sPHN domain no longer required an intact amino-terminal Src homology (SH2N) domain or phosphorylation of tyrosine 775 or 783 for activation. These data are consistent with a model in which the SH2C domain is blocked by an intramolecular interaction(s) that is released upon cellular activation by occupancy of the SH2N domain.Phosphoinositide-specific phospholipase C-␥1 (PLC-␥1) is activated in response to ligand binding by a variety of receptors (2). PLC-␥1 hydrolyzes phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ], leading to the generation of the second messengers, inositol triphosphate (IP 3 ) and diacylglycerol, which release Ca 2ϩ from intracellular stores and activate Ras through the RasGRP/protein kinase C pathway, respectively (8, 13). PLC-␥1 has also been shown to play a role in the activation of NF-B (7). These pathways in turn initiate signaling cascades that culminate in cytokine production, activation of effector function, and cell proliferation (2, 5). The central role of PLC-␥1 in cellular function is further illustrated by the fact that inactivation of the PLC-␥1 gene in mice is embryonic lethal (16).Regulation of PLC-␥1 activity is complex. In quiescent cells, cytosolic sequestration of PLC-␥1 limits access to PI(4,5)P 2 in the plasma membrane. Cell stimulation induces membrane recruitment of PLC-␥1 and its tyrosine phosphorylation, essential steps in PLC-␥1 activation (2,23,36). Key components of PLC-␥ that are involved in these activation events are located within a region unique to PLC-␥ between the X and Y portions of the catalytic domain. This area is composed of two Src homology 2 (SH2) domains and an Src homology 3 (SH3) domain. The N-terminal SH2 domain (SH2N) is critical for binding to either tyrosine-phosphorylated receptor kinases or adaptor molecules that mediate PLC-␥1 relocation to the plasma membrane (6,14,25). The function of the C-terminal SH2 domain (SH2C) is less clear but is also essential for PLC-␥1 activation (1, 6, 14, 33). Interestingly, the tyrosine residues that are essential for PLC-␥1 activity (Y775 and Y783 in PLC-␥1 and Y753 and Y759 in PLC-␥2) are also located in this region (29,30).Components of the SH region not only are essential for PLC-␥1 activation but also may participate in its autoregulation. The individual X or Y elements of the catalytic domain alone are inactive. When mixed together in vitro, the hydrolytic activity of the combined X and Y elements was found...

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“…We examined the possibility of a protein-protein interaction between the PH domain and the CTD of ADL6 as a means by which the CTD could affect the lipid binding specificity of the PH domain. Recently it has been shown that the PH domain is also involved in protein-protein interactions (39,40). Interestingly, there was a strong interaction between the PH domain and the CTD at low salt concentrations.…”

Section: Fig 2 Expression and Purification Of Recombinant Proteinsmentioning

confidence: 99%

The Intermolecular Interaction between the PH Domain and the C-terminal Domain of Arabidopsis Dynamin-like 6 Determines Lipid Binding Specificity

Lee

Jin

Song

et al. 2002

Journal of Biological Chemistry

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Dynamin and its related proteins are a group of mechanochemical proteins involved in the modulation of lipid membranes in various biological processes. Here we investigate the nature of membrane binding of the Arabidopsis dynamin-like 6 (ADL6) involved in vesicle trafficking from the trans-Golgi network to the central vacuole. Fractionation experiments by continuous sucrose gradients and gel filtration revealed that the majority of ADL6 is associated with membranes in vivo. Amino acid sequence analysis revealed that ADL6 has a putative pleckstrin homology (PH) domain. In vitro lipid binding assays demonstrated that ADL6 showed high affinity binding to phosphatidylinositol 3-phosphate (PtdIns-3-P) and that the PH domain was responsible for this interaction. However, the PH domain alone binds equally well to both PtdIns-3-P and phosphatidylinositol 4-phosphate (PtdIns-4-P). Interestingly, the high affinity binding of the PH domain to PtdIns-3-P was restored by a protein-protein interaction between the PH domain and the C-terminal region. In addition, deletion of the inserted regions within the PH domain results in high affinity binding of the PH domain to PtdIns-3-P. These results suggest that ADL6 binds specifically to PtdIns-3-P and that the lipid binding specificity is determined by the interaction between the PH domain and the Cterminal domain of ADL6.

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Interaction of Elongation Factor-1α and Pleckstrin Homology Domain of Phospholipase C-γ1 with Activating Its Activity

Cited by 46 publications

References 45 publications

Proteomics Analysis of Rat Brain Postsynaptic Density

Proteomics Analysis of Rat Brain Postsynaptic Density

Intramolecular Regulation of Phospholipase C-γ1 by Its C-Terminal Src Homology 2 Domain

The Intermolecular Interaction between the PH Domain and the C-terminal Domain of Arabidopsis Dynamin-like 6 Determines Lipid Binding Specificity

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