• c-Src can be activated by many transmembrane proteins that include: adhesion receptors, receptor tyrosine kinases, G-protein coupled receptors and cytokine receptors. (wikipedia.org)
  • Most studies have looked at the receptor tyrosine kinases and examples of these are platelet derived growth factor receptor (PDGFR) pathway and epidermal growth factor receptor (EGFR). (wikipedia.org)
  • EGFR belongs to the HER/ERbB family of proteins that includes three other receptor tyrosine kinases, ERbB2, ERbB3, ERbB4. (thermofisher.com)
  • The EGFR family: not so prototypical receptor tyrosine kinases. (medlineplus.gov)
  • Receptor tyrosine kinases have important roles in the development and progression of human tumors [ 8 ]. (medsci.org)
  • Together with other receptor tyrosine kinases, PDGFRA, is a prominent target not only in gliomas, but also in a number of haematological malignancies for targeted therapies based on tyrosine kinase inhibitors (TKI) and anti-PDGFRA monoclonal antibodies. (biospace.com)
  • Receptor tyrosine kinases (RTKs) play an important role in a variety of cellular processes in cancer [ 3 ]. (hindawi.com)
  • The receptor tyrosine kinases KIT and FLT3 are both important regulators of development and maintenance of a number of different cell types. (lu.se)
  • The role of human EGFR2 (HER2), a member of the ERBB family of tyrosine kinase receptors, has been studied for NSCLC. (medscape.com)
  • Eph receptors represent the largest known family of receptors tyrosine kinases and are broadly divided into subclasses, EphA and EphB. (medsci.org)
  • The EphA receptors (A1-A9) bind to EphrinA ligands, a group of glycosyl phosphatidylinositol-linked membrane proteins and EphB receptors (B1-B6) interact with EphrinB ligands [ 9 ]. (medsci.org)
  • Family A receptors (EPHA) and ligands (EFNA) can act as oncogenes or tumor suppressors and are implicated in chemoresistance. (hindawi.com)
  • Both receptors and ligands are membrane-bound proteins that require direct cell-cell interaction for activation. (hindawi.com)
  • 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)
  • The most promising fragments were successfully used to replace the phospho-tyrosine and resulted in novel nonpeptidic high affinity inhibitors. (rcsb.org)
  • Initial studies with the EGFR tyrosine kinase inhibitors (TKIs) gefitnib (Iressa) and erlotinib (Tarceva) demonstrated biologic and clinical activity in only a relatively limited subset of lung cancers. (medscape.com)
  • Recently, highly targeted small-molecule agents, such as tyrosine kinase inhibitors (TKI), open a new avenue for RA therapy with improved clinical responses ( Koenders and Van DenBerg, 2015 ). (frontiersin.org)
  • Antagonism of SET using OP449 enhances the efficacy of tyrosine kinase inhibitors and overcomes drug resistance in myeloid leukemia. (jefferson.edu)
  • Protein tyrosine phosphatase receptor delta (PTPRD) is a member of a large family of protein tyrosine phosphatases which negatively regulate tyrosine phosphorylation. (biomedcentral.com)
  • Phosphorylation of EGFR at certain residues is also mediated by Src-non-receptor kinase. (thermofisher.com)
  • Phosphorylation of EGFR at Y1086 specifically allows binding of the adaptor protein GRB2, leading to activation of the MAPK pathway. (thermofisher.com)
  • Phosphorylation of the Mdm2 oncoprotein by the c-Abl tyrosine kinase regulates p53 tumor suppression and the radiosensitivity of mice. (umassmed.edu)
  • Mdm2 Phosphorylation Regulates Its Stability and Has Contrasting Effects on Oncogene and Radiation-Induced Tumorigenesis. (umassmed.edu)
  • Binding of Sema4D to plexin-B1 stimulates the intrinsic tyrosine kinase activity of ErbB-2, resulting in the phosphorylation of both plexin-B1 and ErbB-2. (rupress.org)
  • By a broad mass spectrometry based approach on whole cells we are in the process of identifying additional such proteins and their phosphorylation status. (lu.se)
  • Mutations in epidermal growth factor receptor ( EGFR ), KRAS, and anaplastic lymphoma kinase ( ALK ) are mutually exclusive in patients with NSCLC, and the presence of one mutation in lieu of another can influence response to targeted therapy. (medscape.com)
  • Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein and member of the protein kinase superfamily that regulates cell growth and differentiation. (biolegend.com)
  • EGFR is a transmembrane receptor and binding of its cognate ligands such as EGF (Epidermal Growth Factor) and TGF alpha (Transforming Growth Factor alpha) to the extracellular domain leads to EGFR dimerization followed by autophosphorylation of the tyrosine residues in the cytoplasmic domain. (thermofisher.com)
  • Mutations in the EGFR gene are associated with lung cancer and multiple alternatively spliced transcript variants encode different protein isoforms of EGFR have been found. (thermofisher.com)
  • The EGFR gene provides instructions for making a receptor protein called the epidermal growth factor receptor, which spans the cell membrane so that one end of the protein remains inside the cell and the other end projects from the outer surface of the cell. (medlineplus.gov)
  • Lung cancers with EGFR gene mutations tend to respond to treatments that specifically target the overactive epidermal growth factor receptor protein that allows cancer cells to constantly grow and divide. (medlineplus.gov)
  • This gene was initially identified as a homolog of the feline sarcoma viral oncogene v-kit and is often referred to as proto-oncogene c-Kit. (nih.gov)
  • This gene is a member of the protein-tyrosine kinase oncogene family. (cancerindex.org)
  • FYN is a member of the protein-tyrosine kinase oncogene family. (thermofisher.com)
  • It belongs to a family of Src family kinases and is similar to the v-Src (viral Src) gene of Rous sarcoma virus. (wikipedia.org)
  • Among activating class III receptor tyrosine kinase (Flt3) mutations, internal tandem duplications of Flt3 (Flt3-ITD) are detected in about 25% of patients with acute myeloid leukemia (AML). (nih.gov)
  • In contrast, mutations within the tyrosine kinase domain of Flt3 (Flt3-TKD mutations) are less frequent (approximately 7%), and there are only limited data on the frequency of recently demonstrated activating Flt3 point mutation at codon 592 (Flt3-V592A mutation). (nih.gov)
  • Possible mechanisms for developing acquired resistance to anti-cancer drugs include mutations of genes encoding proteins that are the targets of drugs or are present in downstream pathways of proteins inhibited by drugs as well as the activation of collateral pathways ( 19 , 20 ). (spandidos-publications.com)
  • Scope includes mutations and abnormal protein expression. (cancerindex.org)
  • Different cancer types tend to depend on a limited number of 'driver' oncogene mutations. (cancerquest.org)
  • Deregulation of these tyrosine kinases by mutations has been implicated in various human malignancies, including leukemia and melanoma. (lu.se)
  • SCF R is also known as the c-kit proto-oncogene protein and as CD117. (rndsystems.com)
  • Over-expression of the c-erbB-2 oncogene occurs in a proportion of human adenocarcinomas and in breast carcinoma is associated with poorer prognosis. (nih.gov)
  • Sections of formalin-fixed, paraffin-embedded tumour tissue from 22 patients with mammary and extramammary Paget's disease have been stained immunohistochemically using a monoclonal antibody (NCL-CB11) raised against a synthetic peptide from the C-terminal end of the predicted sequence of the c-erbB-2 protein product. (nih.gov)
  • Here, we show that plexin-B family members stably associate with the receptor tyrosine kinase ErbB-2. (rupress.org)
  • c-Src phosphorylates specific tyrosine residues in other tyrosine kinases. (wikipedia.org)
  • Ectopic up-regulation of PTPRD in neuroblastoma dephosphorylates tyrosine residues in AURKA resulting in a destabilization of this protein culminating in interfering with one of AURKA's primary functions in neuroblastoma, the stabilization of MYCN protein, the gene of which is amplified in approximately 25 to 30% of high risk neuroblastoma. (biomedcentral.com)
  • Recombinant protein corresponding to amino acid residues 1-206 of murine p59fynprotein. (thermofisher.com)
  • As a molecular mechanism, we demonstrate that PTPRD interacts with aurora kinase A (AURKA), an oncogenic protein that is over-expressed in multiple forms of cancer, including neuroblastoma. (biomedcentral.com)
  • Deregulated activity of the Abl protein tyrosine kinase is oncogenic in humans and in animals. (torvergata.it)
  • The activation loop tyrosine 823 is essential for the transforming capacity of the c-Kit oncogenic mutant D816V. (lu.se)
  • Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. (joplink.net)
  • This positioning allows the receptor to attach (bind) to other proteins, called ligands, outside the cell and to receive signals that help the cell respond to its environment. (medlineplus.gov)
  • A receptor tyrosine kinase that transduces signals from EXTRACELLULAR MATRIX to the CYTOPLASM by binding ligands such as GALECTIN 3. (bvsalud.org)
  • The ligands can have a glycosylphosphatidylinositol anchor (A type) or a membrane-spanning protein domain (B type). (hindawi.com)
  • Anaplastic lymphoma kinase (ALK) protein may be detected in most cases (60-70%) of systemic ALCL by immunohistochemistry. (medscape.com)
  • Lenvatinib, a multi‑kinase inhibitor, serves a crucial role in the treatment of unresectable hepatocellular carcinoma (HCC). (spandidos-publications.com)
  • Lenvatinib is an oral multi-kinase inhibitor that inhibits mainly vascular endothelial growth factor receptor 1-3, fibroblast growth factor receptor (FGFR) 1-4, platelet-derived growth factor receptor (PDGFR) α, c-KIT, and RET ( 11 ). (spandidos-publications.com)
  • In terms of the disease control rate (complete response + partial response + stable disease ratio), response rate (complete response + partial response ratio), median progression-free survival, and median time to progression, lenvatinib shows significantly better results compared with sorafenib, another oral multi-kinase inhibitor (75.5 vs. 60.5%, 24.1 vs. 9.2%, 7.4 vs. 3.7 months, 8.9 vs. 3.7 months, respectively) ( 7 ). (spandidos-publications.com)
  • When Src is inactive, the phosphorylated tyrosine group at the 527 position interacts with the SH2 domain which helps the SH3 domain interact with the flexible linker domain and thereby keeps the inactive unit tightly bound. (wikipedia.org)
  • The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the fyn-binding protein. (cancerindex.org)
  • Several chimeric murine retroviruses were constructed to test whether the gag sequence of Abelson murine leukemia virus (A-MuLV) could influence the in vitro specificity of two sarcoma-inducing oncogenes: src of Rous sarcoma virus and fps of Fujinami sarcoma virus. (duke.edu)
  • We report here a novel subseries of C-5-substituted anilinoquinazolines that display high affinity and specificity for the tyrosine kinase domain of the c-Src and Abl enzymes. (rcsb.org)
  • pronounced "sarc", as it is short for sarcoma), is a non-receptor tyrosine kinase protein that in humans is encoded by the SRC gene. (wikipedia.org)
  • Eventually this normal gene mutated into an abnormally functioning oncogene within the Rous sarcoma virus. (wikipedia.org)
  • Several Ephrin A (EPHA/EFNA) family members are overexpressed or downregulated in a variety of tumors, suggesting that they act as oncogenes or as tumor suppressors according to the cellular context [ 9 ]. (hindawi.com)
  • A useful analogy to consider when thinking about tumor suppressors and oncogenes is an automobile. (cancerquest.org)
  • 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)
  • Rearranged during transfection (RET), kinase alterations, which include fusions and activating point mutation, lead to overactive RET signaling and uncontrolled cell growth. (medscape.com)
  • The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. (joplink.net)
  • Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. (joplink.net)
  • This induces long-range allostery via protein domain dynamics, causing the structure to be destabilized, resulting in the opening up of the SH3, SH2 and kinase domains and the autophosphorylation of the residue tyrosine 416. (wikipedia.org)
  • Upon activation by its cytokine ligand, stem cell factor (SCF), this protein phosphorylates multiple intracellular proteins that play a role in in the proliferation, differentiation, migration and apoptosis of many cell types and thereby plays an important role in hematopoiesis, stem cell maintenance, gametogenesis, melanogenesis, and in mast cell development, migration and function. (nih.gov)
  • These compounds exhibit high selectivity for SFKs over a panel of recombinant protein kinases, excellent pharmacokinetics, and in vivo activity following oral dosing. (rcsb.org)
  • Two transcript variants encoding the same protein have been found for this gene. (wikipedia.org)
  • Previous studies have demonstrated that DNA damage-inducible transcript 4 (DDIT4), Trib3 (tribbles pseudo kinase 3), alpha-synuclein (α-syn) are involved in METH-induced dopaminergic neurotoxicity. (cancerindex.org)
  • The X-ray data show that the fragments are recognized by forming a complex H-bond network within the phospho-tyrosine pocket of SH2. (rcsb.org)
  • We also measured the levels of phosphorylated tuberous sclerosis complex 2 (TSC2) protein and Parkin protein level in SH-SY5Y cells. (cancerindex.org)
  • 19 normal healthy in- receptor protein (CD117) that is structurally dividuals were recruited as a control group. (who.int)
  • Our results suggest that a screening approach using protein crystallography is particularly useful to identify universal fragments for the conserved hydrophilic recognition sites found in target families such as SH2 domains, phosphatases, kinases, proteases, and esterases. (rcsb.org)
  • c-Src should not be confused with CSK (C-terminal Src kinase), an enzyme that phosphorylates c-Src at its C-terminus and provides negative regulation of Src's enzymatic activity. (wikipedia.org)
  • Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. (joplink.net)
  • N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine (AZD0530) inhibits c-Src and Abl enzymes at low nanomolar concentrations and is highly selective over a range of kinases. (rcsb.org)
  • It has been reported that lung cancer cells exhibit upregulated expression of all key glycolytic enzymes [hexokinase 2 (HK2), phosphofructokinase and pyruvate kinase (PK)] ( 13 ), suggesting that the essential enzymes of the aerobic glycolytic pathway have a critical role in the development of lung carcinoma. (spandidos-publications.com)
  • Several different variants of the bcr-abl fusion proteins occur depending upon the precise location of the chromosomal breakpoint. (jefferson.edu)
  • The activation of c-Src causes the dephosphorylation of the tyrosine 527. (wikipedia.org)
  • These changes led to the constitutive activation of a prominent oncogene - receptor tyrosine kinase gene PDGFRA. (biospace.com)
  • Abl-enhanced maturation was normal as judged by accumulation of Mos as well as activation of MAP kinase and Cdc2/CyclinB (MPF). (torvergata.it)
  • Concomitant with maturation and activation of these kinases, Abl became extensively phosphorylated. (torvergata.it)
  • The canonical form of this glycosylated transmembrane protein has an N-terminal extracellular region with five immunoglobulin-like domains, a transmembrane region, and an intracellular tyrosine kinase domain at the C-terminus. (nih.gov)
  • TPD drugs are an emerging modality that selectively targets disease-causing proteins by leveraging intracellular protein degradation mechanisms, such as the ubiquitin-proteasome system and autophagy. (pharmaceutical-technology.com)
  • Given the versatility inherent in this intrinsically disordered region, its multisite phosphorylations, and its divergence within the family, the unique domain likely functions as a central signaling hub overseeing much of the enzymatic activities and unique functions of Src family kinases. (wikipedia.org)
  • Src family kinases (SFKs) are nonreceptor tyrosine kinases that are reported to be critical for cancer progression. (rcsb.org)