• Growth factors (also known as trophic factors) bind to cell-surface receptors to initiate signaling pathways that result in the growth and differentiation of numerous different cell types. (tocris.com)
  • Although growth factors act on different cell types, the signal pathways they initiate often overlap: for example, both EGF and FGF ensure cell survival by activating PI 3-K and MAPK cascades. (tocris.com)
  • Key signaling pathways are highlighted, and the regulation of ES cell self-renewal and somatic cell reprogramming is discussed. (tocris.com)
  • These events are influenced by and activate other molecular pathways, including phosphatidylinositol 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and mitogen-activated protein kinase (MAPK),[2] and therapies are now available that target these pathocellular processes. (cancernetwork.com)
  • Several pathways of phagocytic signal transduction have been identified [ 3345 ], including the activation of tyrosine kinases or serine/threonine kinase C, leading to phosphorylation of the receptors and other proteins which are recruited at the sites of phagocytosis. (nanomedicine.com)
  • Integrin engagement by ECM can modulate growth factor signaling pathways, increasing the activity of growth factor RTKs (7, 8) and their downstream intracellular mediators (9, 10). (123dok.org)
  • Investigating the downstream transduction pathways revealed key molecular targets underpinning decorin-mediated cell cycle arrest and tumorigenic and angiogenic suppression. (jefferson.edu)
  • CaR stimulation leads to the activation of multiple signal transduction pathways. (jneurosci.org)
  • Specifically, novel protein interactors and signaling pathways for FGFR3 identified through yeast two-hybrid screening are under investigation. (uci.edu)
  • How CXCR4 signaling integrates with other relevant oncogenic transduction pathways and the role of GPCR regulatory mechanisms in such contexts are not well-understood. (nih.gov)
  • Our data point to a role for GRK2 in the crosstalk of the CXCR4 and EGFR signal transduction pathways in pathological contexts characterized by concurrent overactivation of these proteins. (nih.gov)
  • It can reduce the sulfation of cell surface heparan sulfate proteoglycan (HSPG) and inhibit various growth factor receptor-mediated signaling pathways. (oncotarget.com)
  • 1. Role of the cytokine-signal transduction pathways and epigenetic gene silencing in pathogenesis of T-cell lymphoma. (upenn.edu)
  • They indicate that pathways involving STAT3, PI3K/AKT and, apparently, STAT5 are constitutively activated by this kinase. (upenn.edu)
  • This pathway is usually a Dimebon dihydrochloride key mechanism for cell survival in CLL.4 5 Upon activation of the BCR tyrosine kinase Lyn phosphorylates and activates Syk leading to activation of downstream signaling pathways and upregulation of anti-apoptotic proteins such as Mcl-1. (sciencepop.org)
  • The GFRα and GFRα-mediated signaling pathways. (medsci.org)
  • Upregulate the expression in various malignant diseases, and play a role in promoting cancer proliferation, tumor survival and metastasis by activating JAK / STAT3, RAS / ERK, PI3K / mTOR and other signaling pathways. (creative-proteomics.com)
  • Targeting IL-11, IL-11R and gp130 and other IL-11 Drugs that treat the target and its downstream signaling pathways (such as JAK / STAT3, RAS / ERK, and PI3K / mTOR) can provide new options for the treatment of IL-11-related tumors. (creative-proteomics.com)
  • Thus, we suggest that SOCS2 associates with activated FLT3 and negatively regulates the FLT3 signaling pathways. (lu.se)
  • Phospho-proteomics analysis and Western blots are used to demonstrate downstream signaling pathways of PIK3CA/p110α tyrosine phosphorylation. (biomedcentral.com)
  • Correlation analysis showed that DOX-induced HF mainly affected phenylalanine, tyrosine, and tryptophan biosynthesis, D-glutamine and D-glutamate metabolism, phenylalanine metabolism, biosynthesis of unsaturated fatty acids, and other metabolic pathways, suggesting abnormal amino acid metabolism, fatty acid metabolism, and glycerol phospholipid metabolism. (frontiersin.org)
  • Therefore, SLE is currently believed to be a T cell-driven condition and, indeed, targeting molecules expressed on T cells and their signalling pathways can be one of the potential therapeutic strategies in SLE. (hindawi.com)
  • Stimulation of TCRs upon antigen binding triggers downstream signalling pathways which enables various physiological functions of the T cells. (hindawi.com)
  • These abnormalities result in significant alterations in gene expression related to cell proliferation, apoptosis, migration and immune signaling pathways. (spandidos-publications.com)
  • This gene is similar to the sem-5 gene of Caenorhabditis elegans, which is involved in the signal transduction pathway. (wikipedia.org)
  • It also phosphorylates and activates PLCG1 and the PKC signaling pathway. (icr.ac.uk)
  • Involved in interleukin-3/IL3-mediated signaling pathway in basophils (By similarity). (icr.ac.uk)
  • In the developing male (XY) gonad, sex-determining region of the Y (SRY) protein acts to up-regulate expression of the related gene, SOX9 , a transcriptional regulator that in turn initiates a downstream pathway of testis development, whilst also suppressing ovary development. (plos.org)
  • Here we report a role for the phylogenetically ancient mitogen-activated protein kinase (MAPK) signalling pathway in mouse sex determination. (plos.org)
  • This mutant, which we called boygirl ( byg ), was shown to contain an early stop codon that disrupts the autosomal gene encoding MAP3K4, a component of the mitogen-activated protein kinase (MAPK) signaling pathway. (plos.org)
  • One downstream pathway that modified the Ret (MEN2) phenotype was the Src signaling pathway. (grantome.com)
  • Importantly, reducing activity of the STAT signaling pathway prevented this oncogenic growth: mutations in Drosophila STAT led to death of otherwise proliferative Csk tissue. (grantome.com)
  • Overexpression of SLAMF1 or SLAMF7 in IGHV mutated CLL cell models resulted in reduced proliferation and impaired responses to BCR ligation, whereas the knockout of both receptors showed opposing effects and increased sensitivity toward inhibition of components of the BCR pathway. (nature.com)
  • Detailed molecular analyzes showed that SLAMF1 and SLAMF7 receptors mediate their BCR pathway antagonistic effects via recruitment of prohibitin-2 (PHB2) thereby impairing its role in signal transduction downstream the IGHV-mutant IgM-BCR. (nature.com)
  • In the present work, we investi-gated the pathway involved in integrin-mediated activation of RON. (123dok.org)
  • The ↑[Ca 2+ ] i activates a signaling cascade that involves, sequentially, calcium-calmodulin, nitric oxide synthase, guanylyl cyclase, and protein kinase G. This signal transduction pathway enables Cl − to pass through vesicular channels and act as a counterion for the transport of H + , so that the vesicles of secretogogue-stimulated cells become acidic. (jneurosci.org)
  • Signaling through the phosphatidylinositol 3′-kinase (PI3K) pathway is crucial for metabolic responses to insulin, and defects in PI3K signaling have been demonstrated in type 2 diabetes. (diabetesjournals.org)
  • PTEN (MMAC1) is a lipid/protein phosphatase that can negatively regulate the PI3K pathway by dephosphorylating phosphatidylinositol (3,4,5)-triphosphate, but it is unclear whether PTEN is physiologically relevant to insulin signaling in vivo. (diabetesjournals.org)
  • An important anti-tumor mechanism of hSulf-1 operates by decreasing downstream AKT signaling pathway activity and inhibiting the nuclear import of CDK4. (oncotarget.com)
  • We found that cutaneous T-cell lymphoma cells display activation of the interleukin-2 receptor/cytokine common chain-associated Jak/STAT signal transduction pathway that is transient in the early stage of the lymphoma and constitutive in the late stage of the disease progression. (upenn.edu)
  • This study may result in novel therapies for lymphoma based on selective inhibition of the elements of the IL-2R signal transduction pathway(s) which are preferentially utilized by malignant T cells and/or on induction of re-expression of the epigenetically-silenced SHP-1 gene. (upenn.edu)
  • ZAP-70 overexpression in malignant B cells such as CLL cells enhances the B-cell receptor (BCR) pathway. (sciencepop.org)
  • This mechanism of cell death may be common among the tyrosine kinase inhibitors.26 The evidence that ZAP-70 expression sensitizes cells to gefitinib and that gefitinib targets the BCR pathway both indicate that this drug may have activity in the microenvironment. (sciencepop.org)
  • Importantly, increasing numbers of novel reports suggest that the GFRα-mediated signaling pathway acts as an oncogenic promoter related to tumor proliferation, invasion, and metastasis as well as treatment resistance. (medsci.org)
  • Mechanisms of pathway activation other than mutation have been discovered in recent years, and include overexpression mediated by gene amplification or by amplification of a dinucleotide repeat in the EGFR promoter, mutation of an extracellular region on EGFR generating a mutant protein termed EGFRvIII, and enhanced signaling due to heterodimerization with other members of the EGFR family, particularly overexpression of HER2/HER3. (aacrjournals.org)
  • PI3K/AKT signaling pathway plays important role in tumorigenesis of human cancer. (biomedcentral.com)
  • Mutation at Y317 of p110α reduces the proliferation, migration, and invasion of cancer cells through Src-MLC2 pathway, while mutation at Y508 of p110α impairs AKT signaling. (biomedcentral.com)
  • Therefore, investigating PTMs of PI3K signaling components would give us a better understanding how to regulate this pathway and discover more therapeutic targets for cancer. (biomedcentral.com)
  • Plexins are widely expressed transmembrane proteins that mediate the effects of semaphorins. (rupress.org)
  • Their effects are mediated by plexins, a group of transmembrane proteins. (rupress.org)
  • In addition to plexins, various other proteins have been implicated either as receptors for semaphorins or as components of the semaphorin receptor complex ( Pasterkamp and Kolodkin, 2003 ). (rupress.org)
  • Its two SH3 domains direct complex formation with proline-rich regions of other proteins, and its SH2 domain binds tyrosine phosphorylated sequences. (wikipedia.org)
  • The growth/survival signal is initially carried by these receptor ligands - proteins such as epidermal growth factor (EGF), fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) - which bind cell-surface receptor tyrosine kinases (RTKs). (tocris.com)
  • Additionally, transforming growth factor β signals through receptor serine/threonine kinases (RSTKs) and activates downstream SMAD proteins to regulate the expression of specific genes. (tocris.com)
  • Deregulation of growth factor receptor activity is found in nearly all epithelial tumors, and the expression of mutant forms of growth factor proteins may also lead to cancer . (tocris.com)
  • Widespread domain in signalling and nuclear proteins. (embl.de)
  • In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. (embl.de)
  • The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. (icr.ac.uk)
  • CLL cells with both Un-and high ZAP-70 expression show increased activation of proteins downstream of the BCR such as Akt mitogen-activated protein kinase (MAPK) and NF-(7.0?compared with 8.3?compared with 6.0?with gefitinib and cell death was analyzed Dimebon dihydrochloride by flow cytometry after 24?h. (sciencepop.org)
  • Loss of protective proteins on the cell surface makes the red blood cells of PNH patients sensitive to complement-mediated lysis. (sciencepop.org)
  • Video microscopy technology resolving single molecule movement was employed to monitor the dynamic interaction of membrane-associated signalling proteins with TCR signalling clusters in plasma membrane domains. (biomedcentral.com)
  • These studies tracked the movement of Lck and LAT in the T cell plasma membrane and showed retention of these proteins in the submicron TCR signalling domains and their subsequent release. (biomedcentral.com)
  • Numerous intracellular signalling proteins interact with plasma membrane lipids of the cytoplasmic leaflet via specific lipid headgroup-binding domains. (biomedcentral.com)
  • Mutagenic analysis of EphA2 to dissect the residues necessary for oncogenic signaling. (shro.org)
  • Protein tyrosine kinases are enzymes that catalyze the transfer of phosphate from ATP to tyrosine residues in polypeptides. (aacrjournals.org)
  • Two tyrosine residues, Y317 and Y508, are identified on PIK3CA/p110α. (biomedcentral.com)
  • In the cytoplasm, plays a pivotal role in Signal Transduction via its association with cytokine receptors, which constitutes an initiating step in signaling for many members of the cytokine receptor superfamily including the receptors for growth hormone (GHR) , prolactin (PRLR) , leptin (LEPR) , erythropoietin (EPOR) , granulocyte-macrophage colony-stimulating factor (CSF2) , thrombopoietin (THPO) and multiple interleukins. (caslab.com)
  • The protein encoded by this gene is closely related to STAM, an adaptor protein involved in the downstream signaling of cytokine receptors, both of which contain a SH3 domain and the immunoreceptor tyrosine-based activation motif (ITAM). (nih.gov)
  • Similar to STAM, this protein acts downstream of JAK kinases, and is phosphorylated in response to cytokine stimulation. (nih.gov)
  • Under this project my lab investigates the role of signals mediated through receptor for interleukin-2 (IL-2R) and functionally related cytokine receptors in malignant transformation of T lymphocytes. (upenn.edu)
  • As a high-affinity receptor, IL-11R is composed of ligand binding chain α chain and signal transduction chain gp130 (CD130), and belongs to the type I cytokine receptor family. (creative-proteomics.com)
  • Suppressor of cytokine signaling 2 (SOCS2) associates with FLT3 and negatively regulates downstream signaling. (lu.se)
  • The suppressor of cytokine signaling 2 (SOCS2) is a member of the SOCS family of E3 ubiquitin ligases. (lu.se)
  • SOCS2 is known to regulate signal transduction by cytokine receptors and receptor tyrosine kinases. (lu.se)
  • Dive into the research topics of 'Suppressor of cytokine signaling 2 (SOCS2) associates with FLT3 and negatively regulates downstream signaling. (lu.se)
  • Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. (icr.ac.uk)
  • Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. (icr.ac.uk)
  • activates SYK and mediates neutrophils and macrophages integrin-mediated activation (By similarity). (icr.ac.uk)
  • Upon receptor engagement, decorin briefly activates the receptor resulting in a multitude of intracellular signaling events before triggering receptor internalization and lysosomal degradation. (jefferson.edu)
  • Peripherally administered EPO crosses the blood-brain barrier and activates in the brain anti-apoptotic, anti-oxidant and anti-inflammatory signaling in neurons, glial and cerebrovascular endothelial cells and stimulates angiogenesis and neurogenesis. (biomedcentral.com)
  • The second messenger PIP3 recruits and activates 3-phosphoinositide dependent protein kinase-1 (PDK1) and AKT serine/threonine kinase on the membrane [ 2 ]. (biomedcentral.com)
  • Phosphatidylinositol 3′-kinase (PI3K) is a crucial signaling enzyme whose activity is regulated by a variety of biological stimuli, including insulin ( 1 ). (diabetesjournals.org)
  • PTEN also has phosphoinositide 3′-phosphatase activity and is therefore capable of suppressing PI3K signaling by dephosphorylating PIP3 ( 11 , 12 ). (diabetesjournals.org)
  • Normally, upon the stimulations by growth factors (GFs), the receptor tyrosine kinases (RTKs) are activated, and then recruit PI3K protein complex on the membrane to generate phosphatidylinositol-3,4,5-triphosphate (PIP3) from phosphatidylinositol-4,5-biophosphate (PIP2) [ 2 ]. (biomedcentral.com)
  • The byg mutation is an A to T transversion causing a premature stop codon in the gene encoding MAP3K4 (also known as MEKK4), a mitogen-activated protein kinase kinase kinase. (plos.org)
  • Monomeric GTPases of the Rho and ARF families which are engaged downstream of activated receptors, in cooperation with phosphatidylinositol 4-phosphate 5-kinase and phosphatidylinositol 3-kinase lipid modifying enzymes, can modulate locally the assembly of the submembranous actin filament system leading to particle internalization [ 3345 , 5261 ]. (nanomedicine.com)
  • PF cells were found to express regulatory (p85) and catalytic (p110α and p110β) subunits of phosphatidylinositol 3′-kinase (PI3′-kinase). (jneurosci.org)
  • We demonstrate that protein kinase N (PKN) facilitates mTORC1 signalling by repressing PI3KC2-β-mediated phosphatidylinositol-3,4-bisphosphate synthesis downstream of mTORC2. (nature.com)
  • The GDNF family ligands (GFLs) function through a glycosyl-phosphatidylinositol-(GPI) anchored coreceptor, GDNF family receptor alpha (GFRα), and rearranged during transfection (RET), a well-known receptor tyrosine kinase involved in kidney development, spermatogonial stem cell maintenance, and the development and maintenance of the sympathetic, parasympathetic, and enteric nervous systems [ 1 , 2 ]. (medsci.org)
  • Despite the requirement for a number of transcription factors and secreted signalling molecules in sex determination, intracellular signalling components functioning in this process have not been defined. (plos.org)
  • Involved in intracellular signal transduction mediated by cytokines and growth factors. (nih.gov)
  • We recently identified EphA2, a member of a large family of receptor tyrosine-kinases, as the functional receptor for progranulin. (shro.org)
  • Whereas the standard immunosuppressive agents foster development of PTLDs, the impact of novel immunosuppressive agents from the group of selective inhibitors of TOR serine/treonine kinase such as rapamycin and its derivatives including RAD remains undetermined. (upenn.edu)
  • Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade (By similarity). (icr.ac.uk)
  • Moreover, we describe experiments showing the presence of activated MKK4, a direct target of MAP3K4, and activated p38 in the coelomic region of the XY gonad at 11.5 d post coitum, establishing a link between MAPK signalling in proliferating gonadal somatic cells and regulation of Sry expression. (plos.org)
  • Our data indicate, for the first time, a requirement for MAPK signaling in the developing XY gonad in order to facilitate normal expression of SRY and the downstream testis-determining genes and also suggest that reduced dosage of MAP3K4 may be the cause of a previously described autosomal sex-reversing mutation in the mouse. (plos.org)
  • B cell receptor (BCR) signaling plays a critical role in driving proliferation and survival of the malignant clone in chronic lymphocytic leukemia (CLL), supported by the clinical activity of inhibitors targeted toward BCR-associated kinases [ 1 ]. (nature.com)
  • moreover, PI3′-kinase inhibitors (wortmannin and LY294002) antagonized secretion. (jneurosci.org)
  • When patients whose tumors bear the sensitizing mutations are treated with the tyrosine kinase inhibitors gefitinib or erlotinib, we witness response rates and durations never before reported, including complete responses. (aacrjournals.org)
  • Similarly, the tyrosine kinase inhibitors have limited activity in a variety of tumor types with EGFR overexpression. (aacrjournals.org)
  • The extent to which these paths to EGFR activation will confer sensitivity to the tyrosine kinase inhibitors or to EGFR monoclonal antibodies is being explored. (aacrjournals.org)
  • Tocris offers the following scientific literature for Growth Factor Receptors to showcase our products. (tocris.com)
  • Dr. Morrione has made several important discoveries in determining the role of growth factor receptors in transformation. (shro.org)
  • As to the basis for their collaboration, integrins and growth factor receptors may form macromolecular complexes on the cell membrane (7, 8, 13, 16 -18). (123dok.org)
  • Recent data suggest that integrin association with RTKs might also protect the latter against the activity of phosphatases (17, 19) and/or ensure the correct subcellular juxtaposition of cytoplasmic tails of dimer-ized growth factor receptors (17). (123dok.org)
  • Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. (icr.ac.uk)
  • Mechanistic target of rapamycin (mTOR) kinase functions in two multiprotein complexes: lysosomal mTOR complex 1 (mTORC1) and mTORC2 at the plasma membrane. (nature.com)
  • Considerable controversy arose over the concept that cholesterol/sphingolipid-rich rafts in the T cell plasma membrane serve as a platform for TCR signalling reactions. (biomedcentral.com)
  • Here we review new biophysical and biochemical data which provide an updated picture of the highly dynamic nanometer-sized cholesterol/sphingolipid-rich raft domains stabilised by protein-networks to form TCR signalling platforms in the T cell plasma membrane. (biomedcentral.com)
  • Early T cell signalling reactions are embedded in the complex and dynamic lipid bilayer matrix of the T cell plasma membrane and are critically defined by their lateral compartmentalisation in plasma membrane domains [ 1 , 2 ]. (biomedcentral.com)
  • We will here discuss recent data which provide a detailed picture of the membrane raft characteristics of the plasma membrane domains supporting active TCR signalling protein complexes. (biomedcentral.com)
  • The cytosolic ZAP-70 tyrosine kinase is recruited to the T cell plasma membrane via binding to the tyrosine phosphorylated TCR-complex [ 3 ]. (biomedcentral.com)
  • These complexes assemble into submicron TCR signalling domains in the T cell plasma membrane which were first studied by confocal fluorescence microscopy at the contact zone of a T cell with TCR-activating glass coverslips. (biomedcentral.com)
  • However specific lipid-mediated interactions at the T cell plasma membrane bilayer are also a central functional element in early TCR signalling. (biomedcentral.com)
  • Confocal fluorescence microscopy was employed to monitor the distribution of TCR signalling plasma membrane sites and to relate their distribution to that of clustered raft markers which show resistance to Triton X 100 detergent solubilisation. (biomedcentral.com)
  • The discovery of EphA2 as the functional signaling receptor for progranulin and the identification of novel downstream effectors offer a new avenue for understanding the underlying mechanism of progranulin action and may constitute novel clinical and therapeutic targets not only in bladder cancer but also in mesothelioma, where we have evidence supporting a critical role for the progranulin/EphA2 oncogenic axis in this rare and aggressive neoplasia. (shro.org)
  • Characterization of progranulin-evoked ubiquitination and trafficking of EphA2 and its relevance in modulating receptor oncogenic signals. (shro.org)
  • After his graduate studies in Biochemistry at Universita' degli Studi di Milano, Milan Italy, Dr. Morrione moved to USA in 1993 and he has been working in the field of cancer biology since his postdoctoral training at the Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA in the laboratory of Dr. Renato Baserga, one of the leading experts in IGF-IR oncogenic signaling. (shro.org)
  • For example, activating mutations in the Ret receptor tyrosine kinase can provoke oncogenic diseases such as Multiple Endocrine Neoplasia Type 2 (MEN2). (grantome.com)
  • The NPM/ALK kinase is constitutively activated and highly oncogenic. (upenn.edu)
  • Here we review GFRα biological functions and discussed the evidence indicating whether GFRα signaling complex present novel opportunities for oncogenic intervention and treatment resistance. (medsci.org)
  • During epithelial maturation, a large number of signal transduction molecules are utilized to regulate cell cycle and cell death. (grantome.com)
  • Author Summary A family of cell surface molecules called the HER receptor family plays important roles in normal physiology and cancer. (researchhunt.com)
  • A previous study demonstrated that SLAMF1, SLAMF2, and SLAMF7 receptors are rather downregulated on CLL cells as compared to their normal B cell counterpart [ 12 ], suggesting that high expression of these molecules may have detrimental (e.g., antiproliferative) effects in the CLL context. (nature.com)
  • Two transmembrane EPOR molecules form a homodimer that binds one EPO molecule leading to a conformational change and tight bonding of the two EPOR monomers which in turn activate two Janus family tyrosine kinase 2 (JAK2) molecules which associate with cytoplasmic domain of the EPOR. (biomedcentral.com)
  • Once activated, JAK2 phosphorylates distal parts of receptors which subsequently serve as docking sites for downstream signaling molecules. (biomedcentral.com)
  • Our studies concentrate on identification of downstream effector molecules triggered by the NPM/ALK kinase. (upenn.edu)
  • However, abnormal expression or aberrant activation of these molecules may convert normal growth signals to undesirable signals inducing overgrowth, becoming an important contributor to a variety of human cancers. (medsci.org)
  • In the work presented here, we provide compelling data that SLAMF1 and SLAMF7 receptors may not only enhance immune control of CLL but also negatively regulate BCR signaling and thereby impact sensitivity towards BTK inhibition in the substantial fraction of patients with SLAMF1 or SLAMF7 expressing M-CLL. (nature.com)
  • In the case of receptor-mediated phagocytic binding, dansylcadaverine, amantadine, and rimantadine induce inhibition of endocytosis of complement-coated zymosan particles by human peripheral PMN leukocytes. (nanomedicine.com)
  • PKC involvement can be accounted for by PKCγ and an isoform sensitive to inhibition by pseudoZ, probably PKCζ, which is activated via PI3′-kinase. (jneurosci.org)
  • Measured outcomes included inhibition of ADP induced platelet aggregation employing optical aggregometry of plateletrich plasma , bleeding time, time dependent drug plasma concentrations , principal tolerability , electrocardiogram , vital signal, and clinical laboratory modifications. (tcr-signal.com)
  • In addition, interaction with estrogen receptors has been demonstrated, leading to inhibition of function. (cancerindex.org)
  • This study demonstrates an additional cellular target of IM, not necessarily mediated via known tyrosine kinases, that causes inhibition of TA and cell proliferation. (tau.ac.il)
  • C-terminal Src kinase (Csk) is the major inhibitor of Src signaling. (grantome.com)
  • Furthermore, the combination of the FGFR4 inhibitor BLU-554 and the SRC inhibitor KX2-391 dramatically suppressed ELF4-mediated CRC metastasis. (thno.org)
  • The molecular mechanism of this TOR inhibitor-mediated cell growth suppression is currently under investigation. (upenn.edu)
  • RAS nucleotide is stimulated downstream of activated FGFR4 in a p-PTPN11-dependent manner. (reactome.org)
  • involved in neutrophils and macrophages integrin-mediated activation (By similarity). (icr.ac.uk)
  • The protein encoded by this gene binds receptors such as the epidermal growth factor receptor and contains one SH2 domain and two SH3 domains. (wikipedia.org)
  • The ESCRT-0 complex binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes (By similarity). (nih.gov)
  • However, this paradigm changed upon the discovery that soluble decorin directly binds, with high affinity, to a plethora of cell surface receptor tyrosine kinases that are richly expressed by the tumor microenvironment and parenchyma. (jefferson.edu)
  • PSPN not only binds GFRα4 but also signals in neurons mediated by GFRα1 [ 5 ]. (medsci.org)
  • Approaches to investigate neuronal dysfunction include targeted studies of Htt oligomerization and its role in neurotoxicity, transcriptional dysregulation in the context of chromatin remodeling and epigenetics, protein modifications of the mutant protein that influences its clearance and cellular localization, and altered signal transduction in HD. (uci.edu)
  • Here, potential mechanisms involving alterations in T-cell receptor expressions, postreceptor downstream signalling, epigenetics, and oxidative stress which favour activation of lupus T cells will be discussed. (hindawi.com)
  • Progranulin also stimulates capillary morphogenesis downstream of EphA2 as well as the ability to auto-regulate its own expression. (jefferson.edu)
  • Growth factors initiate numerous different signaling cascades in order to regulate cell differentiation and proliferation. (tocris.com)
  • p110s perform lipid kinase activity, and p85s stabilize and regulate p110s. (biomedcentral.com)
  • Members of the RYK/Derailed family have recently been shown to regulate axon guidance in both Drosophila and mammals by acting as Wnt receptors. (biologists.com)
  • EPO acts by binding to its specific transmembrane receptor (EPOR). (biomedcentral.com)
  • These results uncover a mechanism that couples mTORC2-dependent activation of PKN2 to the regulation of mTORC1-mediated nutrient signalling by local lipid signals. (nature.com)
  • In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. (ucsc.edu)
  • Until recently, the progranulin signaling receptor remained unidentified, precluding a full understanding of progranulin action in tumor cell biology. (shro.org)
  • PTEN (MMAC1/TEP1) is a dual-specificity protein phosphatase involved in signal transduction and tumor suppression ( 9 , 10 ). (diabetesjournals.org)
  • The CXCL12 chemokine receptor CXCR4 belongs to the GPCR superfamily and is often overexpressed in cancer, being involved in tumor progression and metastasis. (nih.gov)
  • Our research group is focused on the characterization of the molecular mechanism of action and regulation of cancer cell signaling with particular emphasis on progranulin function in solid tumors, including bladder and mesothelioma. (shro.org)
  • One important mechanism of carcinogenesis is uncontrolled cell proliferation caused by the excessive activation of cell proliferation signals. (oncotarget.com)
  • By targeting analogous forms of activated Ret to the developing Drosophila retina, an in vivo model was developed to explore the downstream signaling components that are responsible for aspects of the MEN2 disease. (grantome.com)
  • The RNA sequencing was used to explore the downstream targets of ELF4. (thno.org)
  • A key step in HER-mediated signal transduction is the formation of dimer complexes between members of this family. (researchhunt.com)
  • When GFLs bind with GFRα, they form complexes and associate with the RET receptor, subsequently activating downstream signaling. (medsci.org)
  • The mammalian orthologs of Derailed and SRC64B also form complexes, suggesting that Src roles in RYK signaling are conserved. (biologists.com)
  • Growth factor receptor-bound protein 2 also known as Grb2 is an adaptor protein involved in signal transduction/cell communication. (wikipedia.org)
  • However, it is unclear how the activity of plexin-B1 and its downstream effectors is regulated by its ligand Sema4D. (rupress.org)
  • Direct downstream effectors phosphorylated by SYK include VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK. (icr.ac.uk)
  • Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with HGS (ESCRT-0 complex). (nih.gov)
  • Aberrant cell signaling and epigenetic regulation of gene expression in human lymphomas. (upenn.edu)
  • Focal adhesion kinase (FAK) is a one hundred twenty five-kD non-receptor tyrosine kinase that plays a main position in mediating sign transduction by integrins, as effectively as by growth aspect receptors, in the regulation of cell adhesion, migration, proliferation, and differentiation in a range of mobile varieties [12,thirteen,fourteen]. (acthreceptor.com)
  • Overexpression of ELF4 boosted CRC metastasis via transactivating its downstream target genes, fibroblast growth factor receptor 4 (FGFR4) and SRC proto-oncogene, non-receptor tyrosine kinase, SRC . (thno.org)
  • In X-linked SCID, loss of IL-2 receptor (IL-2R) function leads to the loss of a lymphocyte proliferation signal. (medscape.com)
  • The receptor tyrosine kinase FLT3 is of importance for proliferation, survival and differentiation of hematopoietic cells and is frequently mutated in acute myeloid leukemia. (lu.se)
  • Furthermore, SOCS2 expression leads to a decrease in FLT3-ITD-mediated cell proliferation and colony formation. (lu.se)
  • Sonic 125256-00-0125B11 hedgehog (Shh) is a forty five-kDa potent signaling protein that regulates the proliferation, differentiation, and cellular patterning throughout a extensive selection of cell types [2,3]. (acthreceptor.com)
  • hSulf-1 reduces the sulfation of heparan sulfate proteoglycans (HSPGs) in the extracellular matrix and inhibits binding between various cell growth factors and their receptors. (oncotarget.com)
  • However, it is becoming increasingly clear that these factors and their receptors are also widely found to express across many different cancers with further research. (medsci.org)
  • The molecular mechanisms of plexin-mediated signal transduction are still rather unclear. (rupress.org)
  • Molecular characterization of the progranulin/EphA2 signaling axis in bladder cancer and mesothelioma. (shro.org)
  • Dr. Morrione has now joined the Sbarro Institute for Cancer Research and Molecular Medicine and Center for Biotechnology, where he is currently Associate Professor (Research) and Director of the Molecular Mechanisms of Cancer Signal Transduction Program. (shro.org)
  • These data demonstrate that MAP3K4-dependent signalling events are required for normal expression of Sry during testis development, and create a novel entry point into the molecular and cellular mechanisms underlying sex determination in mice and disorders of sexual development in humans. (plos.org)
  • Despite the cited progress in this area of research, the molecular mechanisms underlying growth factor receptor activation by integrins remain to be defined. (123dok.org)
  • Endorepellin is a "dual receptor antagonist" that acts as a molecular tether for simultaneous ligation of VEGFR2 and the 21 integrin. (jefferson.edu)
  • However, since molecular commonalities such as defective signal transduction, aggregation and altered transcription have emerged for diseases that involve aberrant protein folding such as Alzheimer's disease, these efforts have applications to a wide range of neurodegenerative diseases. (uci.edu)
  • Although these receptors are structurally similar, they determine specificity for four ligands-GDNF, Neurturin (NRTN), Artemin (ARTN) and Persephin (PSPN). (medsci.org)
  • The gene product is a member of the nuclear hormone receptor family, a group of transcription factors regulated by small hydrophobic hormones, a subset of which do not have known ligands and are referred to as orphan nuclear receptors. (cancerindex.org)
  • both EGFR and c-Src kinase activities. (123dok.org)
  • Recent data indicate concurrent upregulation in certain tumors of CXCR4, EGF receptor (EGFR), and G protein-coupled receptor kinase 2 (GRK2), a signaling node functionally linked to both receptor types. (nih.gov)
  • We have investigated in a model system the effect of the EGFR and GRK2 status on CXCL12/CXCR4-mediated activation of Gi, the earliest step downstream of receptor activation. (nih.gov)
  • It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. (icr.ac.uk)
  • More recently we determined that the constitutive Jak/STAT activation is due, at least in part, to the lack of expression of SHP-1 phosphatase, which normally down-regulates IL-2R/ c-mediated cell activating signals. (upenn.edu)
  • Fig. 4: PKN2 regulates mTORC1 signalling by controlling PI3KC2-β activity and localization. (nature.com)
  • SOCS2 negatively regulates FLT3 signaling by blocking activation of Erk 1/2 and STAT5. (lu.se)
  • Plexin-B1 has recently been shown to mediate activation of RhoA through a stable interaction with the Rho guanine nucleotide exchange factors PDZ-RhoGEF and LARG. (rupress.org)
  • Also mediates the activation of dendritic cells by cell necrosis stimuli. (icr.ac.uk)
  • Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. (icr.ac.uk)
  • mediates the selectin-dependent activation of SYK by SELPLG. (icr.ac.uk)
  • Carries out a dual function: signal transduction and activation of transcription. (ucsc.edu)
  • The model enables us to quantitatively link HER expression levels to receptor dimerization and activation. (researchhunt.com)
  • While the importance 23277-43-2 IC50 of HER expression levels has been established for clinical prognosis and drug resistance, the mechanistic link between receptor expression, HER activation and downstream consequences is not as clear yet. (researchhunt.com)
  • We identified a subset of Chronic Lymphocytic Leukemia (CLL) patients with high Signaling Lymphocytic Activation Molecule Family (SLAMF) receptor-related signaling that showed an indolent clinical course. (nature.com)
  • Signaling Lymphocytic Activation Molecule Family (SLAMF) receptors are a group of nine type I transmembrane receptors that are mainly expressed on a variety of immune cells. (nature.com)
  • In B cells, this class of receptors has been shown to be expressed in distinct patterns associated with development and activation [ 11 ]. (nature.com)
  • EPO signaling is terminated by activation of phosphatases which dephosphorylate JAK2. (biomedcentral.com)
  • The T cell antigen receptor (TCR) provides the key signal for activation of T lymphocytes to perform their numerous effector functions in adaptive immune responses. (biomedcentral.com)
  • The protein has been shown to interact with retinoid and thyroid hormone receptors, inhibiting their ligand-dependent transcriptional activation. (cancerindex.org)
  • Also acts downstream of some G-protein coupled receptors. (caslab.com)
  • Non-receptor tyrosine kinase involved in various processes such as cell cycle progression, apoptosis, mitotic recombination, genetic instability and histone modifications. (caslab.com)
  • Receptor-mediated endocytosis helps terminate the growth factor signal by internalizing the ligand-receptor complex. (tocris.com)
  • The protein encoded by this gene is an unusual orphan receptor that contains a putative ligand-binding domain but lacks a conventional DNA-binding domain. (cancerindex.org)
  • which promoted receptor activator for nuclear factor B ligand (RANKL). (acthreceptor.com)
  • Here, we show that plexin-B family members stably associate with the receptor tyrosine kinase ErbB-2. (rupress.org)
  • This represents a new function for the SAM domain family, which is well characterized for mediating protein-protein interactions. (embl.de)
  • The HER/ErbB family of receptor tyrosine kinases drives critical responses in normal physiology and cancer, and the expression levels of the various HER receptors are critical determinants of clinical outcomes. (researchhunt.com)
  • ZAP-70 is usually a member of the Syk family of protein tyrosine kinases and is normally involved in signal transduction of the T-cell receptor in T cells. (sciencepop.org)
  • Li Q, Cao Z, Zhao S. The Emerging Portrait of Glial Cell Line-derived Neurotrophic Factor Family Receptor Alpha (GFRα) in Cancers. (medsci.org)
  • Glial cell line-derived neurotrophic factor family receptor alpha (GFRα) members have been widely connected to the mechanisms contributing to cell growth, differentiation, cell migration and tissue maturation. (medsci.org)
  • Here, we show that the non-receptor Src family tyrosine kinases, SRC64B and SRC42A, are involved in WNT5-mediated signaling through Derailed in the Drosophila embryonic central nervous system. (biologists.com)
  • These receptors convert signals received from the extracellular environment into cell decisions such as growth and survival C a process termed signal transduction. (researchhunt.com)
  • Parafollicular (PF) cells secrete 5-HT in response to stimulation of a G-protein-coupled Ca 2+ receptor (CaR) by increased extracellular Ca 2+ (↑[Ca 2+ ] e ). (jneurosci.org)
  • A novel pathogenic mutation on the interleukin-7 receptor has been described in a newborn. (medscape.com)
  • However, mutant RTKs may continue to send proliferative signals even in the absence of growth factor stimulation. (tocris.com)
  • Tyrosine phosphorylated following stimulation by IL-4 and IL- 3 (By similarity). (ucsc.edu)
  • Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and MYC induction. (nih.gov)
  • We suggest that PKC isoforms mediate secretion of 5-HT by PF cells in response to stimulation of the CaR. (jneurosci.org)
  • These drugs block receptor-mediated endocytosis, possibly by their actions on phospholipid metabolism [ 3355 ] or by covalent coupling to cellular membranes [ 3356 ]. (nanomedicine.com)
  • Expression of ALK in malignant T cells is typically due to the t(2;5) translocation resulting in formation of the fusion gene which encodes a 80-kDa hybrid protein that contains portion of the nuclear protein nucleophosmin (NPM) joined to the entire cytoplasmic portion of the receptor tyrosine kinase ALK. (upenn.edu)
  • Studies suggest that the protein represses nuclear hormone receptor-mediated transactivation via two separate steps: competition with coactivators and the direct effects of its transcriptional repressor function. (cancerindex.org)
  • on the kinase activity of both RON itself and c-Src. (123dok.org)
  • Raw data for results from screening kinase activity towards T279 of PI3KC2-β are provided in Supplementary Table 2 . (nature.com)
  • These stories advise tha 16926152 t Shh has a osteogenic and osteoclastogenic activity in osteoblast cells [11], but the downstream signaling of SHH in fracture therapeutic has not been determined. (acthreceptor.com)
  • Little is known about how the kinase activity-deficient RYKs transduce Wnt signals. (biologists.com)
  • Derailed and SRC64B form a complex, which contains catalytically active SRC64B, the formation or stability of which requires SRC64B kinase activity. (biologists.com)
  • In addition, IM demonstrates activity against malignant cells expressing c-kit and platelet-derived growth factor receptor (PDGF-R). The activity of IM in the blastic crisis of CML and against various myeloma cell lines suggests that this drug may also target other cellular components. (tau.ac.il)