The class 1A phosphoinositide 3-kinase (PI3K) beta (PI3Kβ) is functionally unique in the ability to integrate signals derived from receptor tyrosine kinases (RTKs), heterotrimeric guanine nucleotide-binding protein (G-protein)-coupled receptors (GPCRs), and Rho-family GTPases. (elifesciences.org)
Ras signaling can be thought of in simple terms as occuring downstream of receptor tyrosine kinases, triggered by association of adaptor proteins with the phosphorylated cytoplasmic tails of these receptors. (sdbonline.org)
PI3K10
Part of B cell differentiation is controlling c-MYC protein stability and steady-state levels through CD19, which acts as a PAX5 target and downstream effector of the PI3K-AKT-GSK3β axis. (wikipedia.org)
CD19 signaling involves the recruitment and activation of phosphoinositide 3-kinase (PI3K) and later downstream, the activation of protein kinase B (Akt). (wikipedia.org)
To address the possibility that activation of phosphatidylinositol-3-kinase (PI3K) and the mammalian target of rapamycin (mTOR/FRAP), represents one of these pathways, we have examined the effect of simultaneous inhibition of the Ras-MAPK and PI3K-mTOR pathways on transformation of CEF by v-Src. (embl.de)
Previous experiments have not been able to elucidate whether interactions with membrane-tethered proteins primarily control PI3Kβ localization versus directly modulate lipid kinase activity. (elifesciences.org)
To address this gap in our understanding of PI3Kβ regulation, we established an assay to directly visualize and decipher how three binding interactions regulate PI3Kβ when presented to the kinase in a biologically relevant configuration on supported lipid bilayers. (elifesciences.org)
Using single molecule Total Internal Reflection Fluorescence (TIRF) Microscopy, we determined the mechanism controlling membrane localization of PI3Kβ, prioritization of signaling inputs, and lipid kinase activation. (elifesciences.org)
We find that auto-inhibited PI3Kβ must first cooperatively engage a single RTK-derived tyrosine phosphorylated (pY) peptide before it can engage either GβGγ or Rac1(GTP). (elifesciences.org)
Although pY peptides strongly localize PI3Kβ to membranes, they only modestly stimulate lipid kinase activity. (elifesciences.org)
misregulation of the PI3K signaling pathway can result in constitutively high levels of PI(3,4,5)P 3 that are detrimental to cell health. (elifesciences.org)
While much work has been dedicated in determining the factors that participate in the PI3K signaling pathway, how these molecules collaborate to rapidly synthesize PI(3,4,5)P 3 remains an important open question. (elifesciences.org)
Isoform2
Synthesis of new cyclitol compounds that influence the activity of phosphatidylinositol 4-kinase isoform, PI4K230. (embl.de)
Ser/Thr protein kinases such as the Akt/Rac family, the beta-adrenergic receptor kinases, the mu isoform of PKC and the trypanosomal NrkA family. (embl.de)
Guanine1
Regulators of small G-proteins like guanine nucleotide releasing factor GNRP (Ras-GRF) (which contains 2 PH domains), guanine nucleotide exchange proteins like vav, dbl, SoS and Saccharomyces cerevisiae CDC24, GTPase activating proteins like rasGAP and BEM2/IPL2, and the human break point cluster protein bcr. (embl.de)
Intracellular membranes2
The recruitment of specific cytosolic proteins to intracellular membranes through binding phosphorylated derivatives of phosphatidylinositol (PtdIns) controls such processes as endocytosis, regulated exocytosis, cytoskeletal organization, and cell signaling. (embl.de)
Critical for cellular organization, phosphatidylinositol phosphate (PIP) lipids regulate the localization and activity of numerous proteins across intracellular membranes in eukaryotic cells ( Di Paolo and De Camilli 2006 ). (elifesciences.org)
Phosphatases1
Phosphoinositide phosphatases play an essential but as yet not well-understood role in lipid-based signal transduction. (embl.de)
Phosphatidylinositol3
We report here that Sac1p has a specific role in secretion and acts as an antagonist of the phosphatidylinositol 4-kinase Pik1p in Golgi trafficking. (embl.de)
The synthesis, chemical derivatization, and investigation of the inhibitory properties of novel cyclitol derivatives on the phosphatidylinositol 4-kinase enzymes PI4K55 and PI4K230 involved in the phosphatidylinositol cycle are reported. (embl.de)
Serving a critical role in cell signaling, the class I family of phosphoinositide 3-kinases (PI3Ks) catalyze the phosphorylation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ] to generate PI(3,4,5) P 3 . (elifesciences.org)
Mammalian2
CD19 is a 95 kd Type I transmembrane glycoprotein in the immunoglobulin superfamily (IgSF) with two extracellular C2-set Ig-like domains and a relatively large, 240 amino acid, cytoplasmic tail that is highly conserved among mammalian species. (wikipedia.org)
The mammalian genome comprises nuclear DNA (nDNA) derived from both parents and mitochondrial DNA (mtDNA) that is maternally inherited and encodes essential proteins required for oxidative phosphorylation. (regenerativemedicine.net)
Despite the detailed in vitro characterization of the enzymatic properties of yeast Sac1p, the exact cellular function of this protein has remained obscure. (embl.de)
Through these interactions, PH domains play a role in recruiting proteins to different membranes, thus targeting them to appropriate cellular compartments or enabling them to interact with other components of the signal transduction pathways. (embl.de)
Cytoskeletal1
Cytoskeletal proteins such as dynamin (see IPR001401 ), Caenorhabditis elegans kinesin-like protein unc-104 (see IPR001752 ), spectrin beta-chain, syntrophin (2 PH domains) and S. cerevisiae nuclear migration protein NUM1. (embl.de)
Eukaryotic1
Domain commonly found in eukaryotic signalling proteins. (embl.de)
Binds2
The PX domain of Vam7p selectively binds PtdIns-3-P, while the PX domain of the CPK PI-3 kinase selectively binds PtdIns-4,5-P(2). (embl.de)
Mouse protein citron, a putative rho/rac effector that binds to the GTP-bound forms of rho and rac. (embl.de)
Residues1
The cytoplasmic tail contains at least nine tyrosine residues near the C-terminus. (wikipedia.org)
Receptors1
To decipher how amplification of PI(3,4,5)P 3 arises from the relay of signals between cell surface receptors, lipids, and peripheral membrane proteins, we must understand how membrane localization and activity of PI3Ks is regulated by different signaling inputs. (elifesciences.org)
Inositol2
The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. (embl.de)
An inositol-1,3,4,5-tetrakisphosphate (IP4)-sensitive extended PH domain is essential for Gap1 activity, while Ca2+-sensitive C2 domains and a glutamine-rich region contribute equally to full activity in vivo. (sdbonline.org)
Trigger1
Mitochondria are also platforms for antiviral signalling2 and, due to their bacterial origin, mtDNA and other mitochondrial components trigger innate immune responses and inflammatory pathology2,3. (regenerativemedicine.net)
Membrane3
On the cell surface, CD19 is the dominant signaling component of a multimolecular complex including CD21, a complement receptor, CD81, a tetraspanin membrane protein (TAPA-1), and CD225. (wikipedia.org)
Protein modules such as FVYE domains and PH domains that bind specifically to PtdIns 3-phosphate (PtdIns-3-P) and polyphosphoinositides, respectively, can direct such membrane targeting. (embl.de)
In addition, the double mutant (Y42A/L48Q) of the PX domain of Vam7p, reported to cause vacuolar trafficking defects in yeast, has a dramatically decreased level of binding to PtdIns-3-P. These data reveal that the membrane targeting function of the Vam7p PX domain is based on its ability to associate with PtdIns-3-P, analogous to the function of FYVE domains. (embl.de)
Containing PH domain2
Taxonomic distribution of proteins containing PH domain. (embl.de)
Click on the protein counts, or double click on taxonomic names to display all proteins containing PH domain in the selected taxonomic class. (embl.de)
Pathway2
Inhibition of the Ras-MAPK pathway by expression of the dominant-negative Ras mutant HRasN17 or by addition of the MAPK kinase (MEK) inhibitor PD98059 reduced several of these parameters but failed to block transformation. (embl.de)
We showed previously that cytoplasmic release of mtDNA activates the cGAS STING TBK1 pathway resulting in interferon-stimulated gene (ISG) expression that promotes antiviral immunity4. (regenerativemedicine.net)
Peripheral1
The presence of a functional BCR is necessary during antigen-dependent differentiation and for continued survival in the peripheral immune system. (wikipedia.org)
Bind1
The N-terminal C2a domain has been shown to bind phospholipids in a Ca2+-dependent manner (Fukuda, 1996 and Fukuda, 1997), while the role of the C2b domain remains unclear. (sdbonline.org)
Copies1
Expression of one copy of wild type Gap1 under control of the sev enhancer/ promoter cassette ( sevGap1 ) rescues the complete loss-of-function eye phenotype, while creating no phenotypic defects when placed in a wild type background containing two copies of the endogenous Gap1 gene. (sdbonline.org)
Activation1
In cultured primary fibroblasts and cancer cells, the chemotherapeutic drug doxorubicin causes mtDNA damage and release, which leads to cGAS STING dependent ISG activation. (regenerativemedicine.net)
Domains4
It contains at least fifteen exons, four that encode extracellular domain and nine that encode cytoplasmic domains, with a total of 556 amino acids. (wikipedia.org)
Pleckstrin homology (PH) domains are small modular domains that occur in a large variety of proteins. (embl.de)
Pleckstrin is one of the rare proteins to contains two PH domains. (embl.de)
There are 196127 PH domains in 171590 proteins in SMART's nrdb database. (embl.de)
Role1
Paired box transcription factor 5 (PAX5) plays a major role in B cell differentiation from pro B cell to mature B cell, the point at which the expression of non-B-lineage genes is permanently blocked. (wikipedia.org)
Find1
Here, we find that persistent mtDNA stress is not associated with basally activated NF-κB signalling or interferon gene expression typical of an acute antiviral response. (regenerativemedicine.net)
Expression1
During B cell lymphopoiesis, CD19 surface expression starts during immunoglobulin (Ig) gene rearrangement, which coincides during B lineage commitment from hematopoietic stem cell. (wikipedia.org)