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Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 30 for “"PH domain"”.
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Targeting Ph Domain Proteins For Cancer Therapy
… promising targeted therapy. Pleckstrin Homology (PH) domain proteins are one of the biggest protein families in the human proteome. However, no drugs have been achieved to the late development stages, let alone getting to the market. Thus, a deeper understanding of this protein family is required …
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MYO1C Binds to PiP2 With High Affinity Through a Putative Ph Domain
… binding sites within the regulatory and tail domains of this myosin. We found that the tail domain binds tightly and specifically to PIP2 in a non-cooperative manner. It binds with slightly higher affinity to Ins(1,4,5)P3 as well as other inositol phosphates which may act as inhibitors to …
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Redefining the specificity of phosphoinositide-binding by human PH domain-containing proteins
… binding characteristics of Pleckstrin Homology (PH) domain, a lipid-binding domain, with phosphoinositides (phosphatidylinositol phosphates or PIPs), an important class of regulatory phospholipids. PH domains are presumed to bind PIPs, but specific interaction with and regulation by PIPs for most …
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P-REX2 PH Domain Inhibition of PTEN Regulates Transformation, Insulin Signaling, and Glucose Homeostasis
… cancers, antagonizes PI3-kinase signaling by dephosphorylating the second messenger phosphatidylinositol (3,4,5) trisphophate. PTEN expression and enzymatic activity is regulated through various mechanisms, including oxidation, phosphorylation, and protein-protein interactions. Our lab has …
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Regulation of p190RhoGEF by Activated Rho and Rac GTPases: Amplification and Crosstalk
… exchange activity resides in a Dbl homology (DH) domain, which is linked to a pleckstrin homology (PH) domain that subserves various functions. We have crystallized and solved structures of the PH domain from p190RhoGEF bound to either RhoA•GTP or Rac1•GTP. The interfaces between activated Rac1 or …
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Domain-based Bioinformatics Analysis and Molecular Insights for the Autoregulatory Mechanism of Phafin2
Phafin2, an adaptor protein, is involved in various cellular processes, such as apoptosis, autophagy, endosomal cargo transportation, and macropinocytosis. Two domains, namely, PH and FYVE, contribute to Phafin2's cell membrane binding. Phafin2 also contains a poly aspartic acid (polyD) motif in …
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Phosphatidylinositol 3-phosphate binding properties and autoinhibition mechanism of Phafin2
Phafin2 is a member of the Phafin protein family. Phafins are modular with an N-terminal PH (Pleckstrin Homology) domain followed by a central FYVE (Fab1, YOTB, Vac1, and EEA1) domain. Both the Phafin2 PH and FYVE domains bind phosphatidylinositol 3-phosphate [PtdIns(3)P], a phosphoinositide mainly …
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Identification and characterization of genetic interactors of the Rho Guanine-nucleotide exchange factor Pebble in <em>Drosophila</em>
… for the migration of mesoderm cells during Drosophila gastrulation. The spreading of mesoderm cells is controlled by the FGF signalling pathway acting through the FGF receptor Heartless (Htl). Pbl represents an important downstream component of this FGF pathway and activates the Rho GTPase Rac, …
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Activated RhoA Positively Regulates Exchange Activity of PDZ-RhoGEF
… state of the GTPases via their DH/PH domains; this facilitates binding of GTP and activation of the protein. The RGS subfamily of RhoGEFs (RGS-RhoGEFs) act as direct mediators of RhoA activation in response to stimulation of the heterotrimeric G12 and G13 proteins by hormone …
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Cloning, Phenotypic, and Experimental Analysis of Pat-4: The Caenorhabditis Elegans Homologue of Integrin -Linked Kinase
… experimental analysis of pat-4 during the morphogenesis of the excretory canal cell. By completely removing pat-4 expression from the excretory cell, I demonstrate that pat-4 is essential for the active outgrowth and complete extension of the excretory canal processes during embryogenesis and …
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Functional Aspects of Protein Kinase C FRET Probe Performance
… EYFP/GFP2 emission ratio of KCP-1 increases upon phosphorylation, while it decreases in KCP-2. Both probes are reversible. We examined the influence of linker length, charge distribution in particular domains of the probe, and fluorophore dimerization on probe performance. Different FRET pairs, …
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Differential Activity of The Kras Oncogene By Method of Activation: Implications For Signaling and Therapeutic Intervention
… and arrests cells with active KRas in the G1 phase of the cell cycle similar to the deletion of an activated<em> </em>KRas regardless of activating substitution. CNK1 has a PH domain responsible for localizing it to membrane lipids making KRas potentially amenable to inhibition with small …
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Development of novel lysine targeting covalent inhibitors for Bruton’s tyrosine kinase and casein kinase 2 and synthesis of novel hybrid androgen receptor inhibitors
… steps towards the peptidomimetic electrophile are presented, along with the biological characterisation of the final target molecule. Protein mass spectrometry and tandem mass spectrometry studies indicate that the electrophile does not target Lys158, as intended, but that instead it …
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Dual Regulation of Phospholipase C-beta by G betagamma
… release of GDP and binding of GTP to the G alpha subunit (Ga), releasing active Ga and G betagamma (Gbg) subunits. Activated alpha subunits of the Gq family and betagamma subunits of the Gi family stimulate phospholipase C-beta (PLC-b) isoforms to catalyze hydrolysis of …
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The Middle Region is Required for Phosphorylation Regulation of Ceramide Transfer Protein
… (ER), where it is synthesized, to the Golgi for sphingomyelin synthesis is mediated by the ceramide transfer protein (CERT) in a nonvesicular fashion. CERT is a cytosolic protein containing multiple domains and motifs. The START (steroidogenic acute regulatory protein-related lipid transfer) …
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A Phosphoinositide-Specific Phospholipase C of Trypanosoma Cruzi: Unique Characteristics of a Delta-Type Homologue
The phosphoinositide-specific phospholipase C gene (TcPI-PLC  ) of the protozoan parasite Trypanosoma cruzi was cloned, sequenced, expressed in E. coli, and the protein product (TcPI-PLC) was shown to have enzymatic characteristics similar to those of mammalian delta-type PI-PLCs. The …
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Investigation of structural dynamics and the function of membrane proteins with computational techniques
… of accelerated membrane models, which enhanced phospholipid diffusion and reorganization in the membrane using an atomistic representation, we captured repeated and spontaneous insertion of human signalling proteins, in a lipid-dependent manner. More specifically, simulations of GRP1-PH domain …
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Investigating PLEKHS1 adaptor function in PI3K signalling and human cancer biology
… in cancerous, PTEN-null mouse prostate. PTEN phosphatase is a tumour-suppressor and inactivated commonly in prostate cancers. PLEKHS1 is otherwise a poorly characterised protein. This thesis presents research investigating the relevance and mechanisms of PLEKHS1 adaptor protein function to …
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The Novel Role of Interleukin-1 Receptor-Associated Kinase 1 in the Signaling Process Controlling Innate Immunity and Inflammation
… IRAK1-IRS1 biochemical interaction are IRS-1's PH domain and IRAK-1's proline-rich LWPPPP motif. Our studies also indicate that IRAK-1 is involved with the negative regulation of glycogen synthesis through inhibiting PI3K-Akt signaling pathway and thus releasing GSK3β's inhibitory effect on …
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AFAP-110 is a cSrc activator
… transformed cells. Mutation of protein binding domains (SH2 and SH3) from cSrc results in the deregulation of the kinase and the transformation of cells, while deletion of these domains blocks transformation by active forms of Src. This indicates that SH2/SH3 binding partners for cSrc may play a …
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