Looking for online definition of AXL receptor tyrosine kinase in the Medical Dictionary? AXL receptor tyrosine kinase explanation free. What is AXL receptor tyrosine kinase? Meaning of AXL receptor tyrosine kinase medical term. What does AXL receptor tyrosine kinase mean?

TY - JOUR. T1 - Recurrence of anaplastic lymphoma kinase (ALK) positive adenocarcinoma after 17 years. T2 - Case report. AU - Al-Baimani, Khalid. AU - Sekhon, Harman S.. AU - Wheatley-Price, Paul. PY - 2015. Y1 - 2015. N2 - Introduction: About four to six percent of non-small cell lung cancer (NSCLC) harbor Anaplastic lymphoma kinase rearrangement (ALK). ALK positive NSCLC has a distinct clinicopathological features. In the advanced setting ALK tyrosine kinase inhibitors are used in the first and second line of treatment. However, less is known about the outcome of stage one ALK positive NSCLC. Presentation of case: Our case is a 58 year old man who presented initially with stage one ALK positive NSCLC. He relapsed 17 years later. Discussion: It is very unusual for stage one NSCLC to relapse beyond 10 years. It is surprising that our patient relapsed many years after his initial diagnosis. Conclusion: This may highlight a different biology and outcome. It may also mean a longer follow up is ...

This randomized, active controlled, multicenter phase III open-label study is designed to evaluate the efficacy and safety of alectinib compared with crizotinib treatment in participants with treatment-naive anaplastic lymphoma kinase-positive (ALK-positive) advanced non-small cell lung cancer (NSCLC). Participants will be randomized in a 1:1 ratio to receive either alectinib, 600 milligrams (mg) orally twice daily (BID), or crizotinib, 250 mg orally BID. Participants will receive treatment until disease progression, unacceptable toxicity, consent withdrawal or death. The study is expected to last approximately 42 months ...

A Study Comparing Alectinib With Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer Participants - NCT02075840

c met related tyrosine kinase antibody; CD136 antibody; CD136 antigen antibody; CDw136 antibody; Macrophage stimulating 1 receptor (c met related tyrosine kinase) antibody; Macrophage stimulating 1 receptor antibody; Macrophage stimulating protein receptor alpha chain antibody; MACROPHAGE STIMULATING PROTEIN RECEPTOR antibody; Macrophage stimulating protein receptor beta chain antibody; Macrophage-Stimulating 1 Receptor (MST1R) antibody; Macrophage-stimulating protein receptor beta chain antibody; MSP receptor antibody; Mst1r antibody; MST1R variant RON30 antibody; MST1R variant RON62 antibody; NPCA3 antibody; p185 RON antibody; p185-Ron antibody; Protein-tyrosine kinase 8 antibody; PTK 8 antibody; ptk8 antibody; PTK8 protein tyrosine kinase 8 antibody; Recepteur dorigine nantais (RON) antibody; RON antibody; RON protein tyrosine kinase antibody; RON variant E2E3 antibody; RON_HUMAN antibody; Soluble RON variant 1 antibody; Soluble RON variant 2 antibody; Soluble RON variant 3 antibody; Soluble ...

The CCAAT/enhancer-binding protein β (C/EBPβ) plays a major role in the pathogenesis of anaplastic large cell lymphomas (ALCL) that express the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) tyrosine kinase (ALK(+)). Although ALK-mediated C/EBPβ transcriptional activation has been reported, C/EB …

Neuroblastoma is a childhood extracranial solid tumour that is associated with a number of genetic changes. Included in these genetic alterations are mutations in the kinase domain of the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase (RTK), which have been found in both somatic and familial neuroblastoma. In order to treat patients accordingly requires characterisation of these mutations in terms of their response to ALK tyrosine kinase inhibitors (TKIs). Here, we report the identification and characterisation of two novel neuroblastoma ALK mutations (A1099T and R1464STOP), which we have investigated together with several previously reported but uncharacterised ALK mutations (T1087I, D1091N, T1151M, M1166R, F1174I and A1234T). In order to understand the potential role of these ALK mutations in neuroblastoma progression, we have employed cell culture-based systems together with the model organism Drosophila as a readout for ligand-independent activity. Mutation of ALK at position 1174 (F1174I

Anaplastic large cell lymphomas (ALCLs) are CD30-positive T-cell non-Hodgkin lymphomas broadly segregated into ALK-positive and ALK-negative types. Although ALK-positive ALCLs consistently bear rearrangements of the ALK tyrosine kinase gene, ALK-negative ALCLs are clinically and genetically heterogeneous. About 30% of ALK-negative ALCLs have rearrangements of DUSP22 and have excellent long-term outcomes with standard therapy. To better understand this group of tumors, we evaluated their molecular signature using gene expression profiling. DUSP22-rearranged ALCLs belonged to a distinct subset of ALCLs that lacked expression of genes associated with JAK-STAT3 signaling, a pathway contributing to growth in the majority of ALCLs. Reverse-phase protein array and immunohistochemical studies confirmed the lack of activated STAT3 in DUSP22-rearranged ALCLs. DUSP22-rearranged ALCLs also overexpressed immunogenic cancer-testis antigen (CTA) genes and showed marked DNA hypomethylation by reduced ...

Concentrating on anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase receptor initially defined as a potent oncogenic driver in anaplastic large-cell lymphoma (ALCL) by means of nucleophosmin (NPM)-ALK fusion protein, using tyrosine kinase inhibitors shows to be always a appealing therapeutic approach for ALK-expressing tumors. not really well covered. Within this review, the molecular systems of cancers stem cells in mediating level of resistance to ALK inhibitors along with the current knowledge of the molecular issues in concentrating on ALK in ALK-expressing individual cancers is going to be talked about. gene aberrations [6,7]. For instance, the echinoderm microtubule-associated proteins like 4 (fusion was discovered in ~5% of non-small cell lung malignancies (NSCLC) [8,9]. Amplified or mutated was discovered in ~14% of neuroblastomas (NB), the most frequent and aggressive youth malignancy [10,11,12,13]. Up to now, many ALK inhibitors are in various levels of clinical examining and ...

Alt. Names/Synonyms: c-met-related tyrosine kinase; CD136; CDw136; macrophage stimulating 1 receptor (c-met-related tyrosine kinase); Macrophage-stimulating protein receptor; Macrophage-stimulating protein receptor alpha chain; Macrophage-stimulating protein receptor beta chain; MSP receptor; MST1R; p185-Ron; Protein-tyrosine kinase 8; PTK8; PTK8 protein tyrosine kinase 8; RON; soluble RON variant 1; soluble RON variant 2; soluble RON variant 3; soluble RON variant 4 ...

Anaplastic lymphoma kinase (ALK) is a receptor type tyrosine kinase that belongs to the insulin receptor superfamily. It is also known as anaplastic lymphoma receptor tyrosine kinase, Tcrz, CD246, and NBLST3. ALK is expressed in the central and peripheral nervous system at late embryonic stage, and plays an important role in brain development. The ALK gene is rearranged, mutated, or amplified in various tumors, including anaplastic large cell lymphomas, neuroblastoma, and non-small cell lung cancer. This monoclonal antibody (clone mAb16-39) elicits tyrosine phosphorylation of ALK in human neuroblastoma (SK-N-SH) cells. It also induces further phosphorylation of signal transfer molecules like insulin receptor substrate-1 (IRD-1).. ...

The overall response rate was significantly higher with Crizotinib than with chemotherapy ( 83.3% in the Crizotinib vs. 25.0% in the chemotherapy group, P less than 0.05 ); the disease control rates were 100% and 75%, respectively ( P less than 0.05 ...

β-catenin, the critical effector of the Wnt pathway, regulates a number of key processes during development including proliferation, differentiation and cell fate determination, as well as tissue homeostasis in adults. β-catenin is normally localized to the cell adhesion junctions in epithelial cells and its abnormal cytplasmic/nuclear stabilization drives uncontrolled transcription of target genes (including c-jun, cyclin D1, c-myc, survivin, and MMP-7) regulating cell proliferation, survival and cell adhesion.12 In view of its biological importance, it is not surprisingly that deregulation of β-catenin has been linked to the pathogenesis of a number of human cancers, particularly those with an epithelial cell origin.28 Illegitimate activation of β-catenin has also been reported in several types of hematopoietic cancers.19,29-31 Nevertheless, the functional status and biological role of β-catenin have never been investigated in ALK+ALCL. In this study, we found that β-catenin is ...

Background The wounding response relies on tightly regulated crosstalk between recruited fibroblasts and the collagenous extracellular matrix (ECM). Discoidin domain receptor 2 (DDR2) is a tyrosine kinase receptor for fibrillar collagen expressed during pathologic scarring, for example wound healing, arthritis and cancer. We have previously shown that DDR2 phosphorylation drives key wounding responses in skin fibroblasts including proliferation, chemotactic migration and secretion of both metalloproteinases and fibrillar collagen. In this study we compared healing of cutaneous wounds in DDR2+/+ and DDR2-/- mice and analyzed specific fibroblast responses. Results Cutaneous wound healing was significantly delayed in DDR2-/- mice compared with DDR2+/+ animals. Reduced α-smooth muscle actin (αSMA) expression and matrix metalloproteinase 2 (MMP2) activity in the DDR2-/- wound extracts indicated defective recruitment of skin fibroblasts. DDR2-/- wounds showed decreased tensile strength during ...

The wounding response relies on tightly regulated crosstalk between recruited fibroblasts and the collagenous extracellular matrix (ECM). Discoidin domain receptor 2 (DDR2) is a tyrosine kinase receptor for fibrillar collagen expressed during pathologic scarring, for example wound healing, arthritis and cancer. We have previously shown that DDR2 phosphorylation drives key wounding responses in skin fibroblasts including proliferation, chemotactic migration and secretion of both metalloproteinases and fibrillar collagen. In this study we compared healing of cutaneous wounds in DDR2+/+ and DDR2-/- mice and analyzed specific fibroblast responses. Cutaneous wound healing was significantly delayed in DDR2-/- mice compared with DDR2+/+ animals. Reduced α-smooth muscle actin (αSMA) expression and matrix metalloproteinase 2 (MMP2) activity in the DDR2-/- wound extracts indicated defective recruitment of skin fibroblasts. DDR2-/- wounds showed decreased tensile strength during healing, which correlated with a

Macrophage stimulating 1 receptor (c-met-related tyrosine kinase), encoded by the MST1R gene, is a cell-surface receptor that binds macrophage-stimulating protein (MSP). It was previously known as RON. The precursor protein is cleaved to generate the mature form, a heterodimer of disulfide-linked alpha and beta subunits. The beta subunit of MST1R/RON is phosphorylated at tyrosine residues upon activation by MSP. MST1R/RON signaling activates the wound healing response by promoting epithelial cell migration, proliferation, and survival at the wound site. MST1R/RON is also known as CDw136, protein-tyrosine kinase 8 (PTK8), c-met-related tyrosine kinase, macrophage-stimulating protein receptor, MSP receptor, p185-Ron, CD136, MST1R variant RON30, MST1R variant RON62, and RON variant E2E3.. ...

The prognostic impact of minimal disseminated disease (MDD) and anti-anaplastic lymphoma kinase (ALK) antibody titer in children with ALK-positive anaplastic large cell lymphoma (ALCL) was reported...

Receptor tyrosine kinases play a key role in the communication of cells with their microenvironment. These kinases are involved in the regulation of cell growth, differentiation and metabolism. The protein encoded by this gene belongs to a subfamily of tyrosine kinase receptors with homology to Dictyostelium discoideum protein discoidin I in their extracellular domain, and that are activated by various types of collagen. Expression of this protein is restricted to epithelial cells, particularly in the kidney, lung, gastrointestinal tract, and brain. In addition, it has been shown to be significantly overexpressed in several human tumors. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2011 ...

Patients harboring ALK rearrangement adenocarcinoma after acquired resistance to crizotinib and transformation to small-cell lung cancer: a case report You-cai Zhu,1 Xing-hui Liao,2 Wen-xian Wang,3 Chun-wei Xu,4 Wu Zhuang,5 Li-hua Zhong,4 Kai-qi Du,1 Yan-ping Chen,4 Gang Chen,4 Mei-yu Fang6 1Department of Chest Disease Diagnosis and Treatment Center, 2Department of Tumor Molecular Laboratory, Zhejiang Rongjun Hospital, Jiaxing, Zhejiang, 3Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, 4Department of Pathology, Fujian Provincial Cancer Hospital, 5Department of Medical Thoracic Oncology, Fujian Provincial Cancer Hospital, Fujian Medical University Cancer Hospital, Fujian, Fuzhou, 6Department of Comprehensive Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, People’s Republic of China Abstract: Anaplastic lymphoma kinase (ALK) rearrangement responds to ALK tyrosine kinase inhibitors (TKIs) in lung cancer. Many cases ultimately acquire resistance to

The ALK tyrosine kinase receptor is oncogenically activated in neuroblastoma. Whereas numerous ALK fusion genes have been reported in different malignancies, in neuroblastoma ALK is mainly activated through point mutations. Three hotspot residues (F1174, F1245, and R1275) account for 85% of mutant ALK seen in neuroblastoma. In a cohort of 105 Swedish neuroblastoma cases of all stages, these hotspot regions were re-sequenced (> 5000X). ALK mutations were detected in 16 of 105 patients (range of variant allele fraction: 2.7-60%). Mutations at the F1174 and F1245 hotspot were observed in eleven and three cases respectively. ALK mutations were also detected at the I1171 and L1240 codons in one tumor each. No mutations were detected at R1275. Sanger sequencing could confirm ALK status for all mutated samples with variant allele fraction above 15%. Four of the samples with subclonal ALK mutation fraction below this would have gone undetected relying on Sanger sequencing only. No distinct mutation ...

Brigatinib (BGB) is a newly approved anaplastic lymphoma kinase (ALK) inhibitor. On April 28, 2017, BGB was approved by the U.S. FDA for the treatment of metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer. The toxicity profile of BGB includes nausea, fatigue, diarrhea, elevated lipase, dyspno

Zhou YQ, He C, Chen YQ et al. (2003). Altered expression of the RON receptor tyrosine kinase in primary human colorectal adenocarcinomas: generation of different splicing RON variants and their oncogenic potential. Oncogene 22 (2): 186-97. PMID 12527888. doi:10.1038/sj.onc.1206075. CS1 održavanje: Eksplicitna upotreba et al. (link) ...

Introduction Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (in stem cell-like properties and of lincROR and crizotinib resistance in NSCLC cells are yet to become elucidated. important part of lincROR in EMLCALK+ NSCLC. lincROR may serve as a potential restorative focus on to conquer chemotherapy level of resistance in EMLCALK+ NSCLC. ) is usually a transforming gene and a driver mutation in NSCLC, which has been identified to be closely associated with cancerogenesis and serves as a causative factor in patients with NSCLC.5,6 The resulting fusion protein preserves the complete intracellular portion of ALK, and therefore, NSCLC cells with this fusion protein are highly sensitive to AMD3100 irreversible inhibition ALK tyrosine kinase inhibition, which could restrain tumor proliferation and induce tumor apoptosis.7 Crizotinib, a specific ALK inhibitor, is beneficial for most patients with ALK-positive NSCLC but has no obvious therapeutic effect on a minority of ...

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1. Protein Tyrosine Kinase (PTK) family; mammalian Discoidin Domain Receptor 1 (DDR1) and homologs; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR1 is a member of the DDR subfamily, which are receptor tyr kinases (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDR1 binds to all collagens tested to date (types I-IV). It is widely expressed in many tissues. It is abundant in the brain and is also found in keratinocytes, colonic mucosa ...

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1. Protein Tyrosine Kinase (PTK) family; mammalian Discoidin Domain Receptor 1 (DDR1) and homologs; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR1 is a member of the DDR subfamily, which are receptor tyr kinases (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDR1 binds to all collagens tested to date (types I-IV). It is widely expressed in many tissues. It is abundant in the brain and is also found in keratinocytes, colonic mucosa ...

Colorectal cancers harbor many well-known somatic alterations, including mutations in KRAS, PI3K, APC, or p53. Recently, thanks to high-throughput sequencing, RTK alterations have also been characterized, including mutations in the HER2 kinase and translocation of TRKA, found infrequently in colorectal cancer but potentially allowing treatment with TKIs targeting them (20-22). In this study, deep high-throughput sequencing revealed 38 mutations in RTKs, only five of which were already referenced in the COSMIC database. This suggests the existence of various RTK mutations in metastatic colorectal cancer, particularly because they were found in a relatively small cohort of 30 patients. To detect somatic mutations specifically, we chose to sequence genomic DNA from adjacent healthy tissue from all 30 patients to eliminate constitutional mutations from our list. We also sequenced genomic DNA from metastases to obtain information about the persistence of these mutations in metastatic lesions. It is ...

Receptor tyrosine kinases have an individual transmembrane (TM) section thats usually assumed to try out a passive function in ligand-induced dimerization and activation from the receptor. and covalent cross-linking tests. Our findings tension the part of TM website relationships in ErbB receptor function, and perhaps for additional single-spanning membrane protein. Intro Receptor tyrosine kinases (RTKs) are transmembrane (TM) glycoproteins that contain a adjustable extracellular N-terminal website, an individual membrane spanning domains, and a big Mdk cytoplasmic portion made up of a juxtamembrane domains, the extremely conserved tyrosine kinase domains, and a C-terminal regulatory area. Biochemical and structural data concur in todays proven fact that ligand binding stimulates monomeric receptor dimerization and trans-autophosphorylation at described tyrosine residues through intrinsic kinase activity (Heldin, 1995 ; Weiss and Schlessinger, 1998 ; Hubbard, 1999 ). Whereas ligand-induced RTK ...

Growth arrest-specific 6, also known as GAS6, is a human gene coding for the Gas6 protein. It is similar to the Protein S with the same domain organization and 43% amino acid identity. It was originally found as a gene upregulated by growth arrested fibroblasts. Gas6 is a gamma-carboxyglutamic acid (Gla) domain-containing protein thought to be involved in the stimulation of cell proliferation. Gas6 has been shown to interact with AXL receptor tyrosine kinase, MerTK and TYRO3. The presence of Gla needs a vitamin K-dependent enzymatic reaction that carboxylates the gamma carbon of certain glutamic residues of the protein during its production in the endoplasmic reticulum. GRCh38: Ensembl release 89: ENSG00000183087 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000031451 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Entrez Gene: GAS6 growth arrest-specific 6. Mark MR, Chen J, Hammonds RG, Sadick M, Godowsk PJ (Apr 1996). Characterization of Gas6, a member ...

The receptor tyrosine kinase AXL is a pathway that plays a crucial role in metastasis and chemoresistance. Overexpression of AXL has been associated with metastasis, recurrence, and chemoresistance in various cancer including ovarian cancer[16, 17]}. Targeting AXL is an attractive approach because it is overexpressed among patients with epithelial ovarian cancer and strongly associated with advanced stages, high grade cancer and shorter median survival time. AVB-S6-500 is a potent AXL inhibitor by binding to the ligand Gas6. Pre-clinical studies found that AVB-S6-500 was efficacious in ovarian cancer xenograft tumor models. Interventions which would increase the proportion of patients achieving pCR in this patient population could impact survival favorably and are of interest for study ...

Because DDR1 is an RTK, we investigated the role of its kinase activity in invadosome formation. We demonstrated, using nilotinib as an inhibitor as well as blocking antibodies, that DDR1 kinase activity is not necessary for the formation of linear invadosomes. This is in agreement with our previous observations. Indeed, we found that linear invadosomes already appear within 10 min of cell seeding on type I collagen, a kinetic that is not compatible with DDR autophosphorylation, a slow process requiring ,30 min before being detectable (Shrivastava et al., 1997; Vogel et al., 1997; Juin et al., 2012). Interestingly, it was previously shown that the role of DDR1 in promoting collective migration was also independent of its kinase activity (Hidalgo-Carcedo et al., 2011). In our hands, the lack of requirement for c-Src activity, demonstrated with both a pharmacological antagonist and the use of SYF cells, is also in line with these findings because it was shown that c-Src was necessary for the full ...

TY - JOUR. T1 - Ron is a heterodimeric tyrosine kinase receptor activated by the HGF homologue MSP. AU - Gaudino, Giovanni. AU - Follenzi, Antonia. AU - Naldini, Luigi. AU - Collesi, Chiara. AU - Santoro, Massimo. AU - Gallo, Kathleen A.. AU - Godowski, Paul J.. AU - Comoglio, Paolo M.. PY - 1994. Y1 - 1994. N2 - RON, a cDNA homologous to the hepatocyte growth factor (HGF) receptor gene (MET), encodes a putative tyrosine kinase. Here we show that the RON gene is expressed in several epithelial tissues as well as in granulocytes and monocytes. The major RON transcript is translated into a glycosylated single chain precursor, cleaved into a 185 kDa heterodimer (p185(RON)) of 35 (α) and 150 kDa (β) disulfide-linked chains, before exposure at the cell surface. The Ron,β-chain displays intrinsic tyrosine kinase activity in vitro, after immunoprecipitation by specific antibodies. In vivo, tyrosine phosphorylation of p185(RON) is induced by stimulation with macrophage stimulating protein (MSP), a ...

Discoidin Domain Receptor 2 Inhibits Fibrillogenesis of Collagen Type 1 Lucy Greetham Mark Nowey Britney Tappen Lauren Canova Casey Pham Learning Objectives • Identify the objectives of the paper (level 1- Remember) • Distinguish the advantages and disadvantages of in-vivo and in-vitro experimentation to study collagen. (level 2 - Understand) • Demonstrate ability to understand SPR techniques and interpret new data. (level 3 - Apply) • Design an experiment to test your hypothesis for the mechanism of cellular response to a change in DDR expression (level 6 - create) Objectives • What are the main objectives of this paper? - Show interaction between DDR2 and collagen type 1 - Study the binding kinetics - Determine how DDR2 effects fibrilogenesis Discoidin Domain Receptors (DDR1 and DDR2) • Widely expressed cell surface receptors, which bind and are activated by collagen • Activation results in downstream signaling which is known to regulates the ECM • Both bond the native triple ...

Rabbit Polyclonal antibody to AXL (AXL receptor tyrosine kinase)IgGy Antibody Selector - Quickly search hundreds of thousands of antibodies available for purchase from VWR by selecting common antibody features like antigen symbol and name, reactivity, clonality, conjugation, host, and other key factors. Antibodies used to identify and locate intracellular and extracellular proteins in common applications such as Western Blot, ELISA, ImmunoChemistry and Flow Cytometry are all available for your research.

Receptor proteins are located within the cell surface membrane, nucleus membrane or other cellular organelle membrane. They can bind to corresponding ligands to initiate cellular signaling pathways. For cell surface receptors, such as receptor tyrosine kinases, interleukin receptors and receptors of growth factors, they are usually subdivided into three domains, extracellular domain, transmembrane domain and intracellular domain. Receptor proteins form the largest family of biological targets. For example, GPCR (G protein coupled receptor) is the target of more than 50% of current drugs. GPCR family members share a unique structure with seven-transmembrane domains. Receptor tyrosine kinases are single transmembrane proteins. They are key regulators for normal cellular processes and also involved in developing many types of cancer. The extracellular part of receptor tyrosine kinases is responsible for binding to growth factors and cytokines. The intracellular domain has kinase activity. Many ...

The EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) fusion-type tyrosine kinase is an oncoprotein found in 4 to 5% of non-small-cell lung cancers, and clinical trials of specific inhibitors of ALK for the treatment of such tumors are currently under way. Here …

Developed to target the anaplastic lymphoma kinase (ALK) mutation, Xalkori (crizotinib) was approved for a subset of non-small cell lung cancers. The ALK mutation is also present in more than half of anaplastic large-cel

WASHINGTON & CAMBRIDGE, Mass., Apr 20, 2010 (BUSINESS WIRE) --ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced results of preclinical studies on its investigational anaplastic lymphoma kinase (ALK) inhibitor - AP26113 - showing potent inhibition of the target protein and of mutant forms that are resistant to the first-generation ALK inhibitor, which currently is in clinical trials in patients with cancer. ARIAD scientists presented these data today at the annual meeting of the American Association for Cancer Research (AACR) in Washington, D.C. Genetic studies indicate that abnormal expression of ALK is a key driver of certain types of non-small cell lung cancer (NSCLC) and neuroblastomas, as well as anaplastic large cell lymphoma. Since ALK is generally not expressed in normal adult tissues, it represents a highly promising molecular target for cancer therapy. An in vitro assay was used to identify mutations in ALK that confer resistance to the investigational dual Met/ALK inhibitor ...

A standard therapy for breast cancer is the use of receptor tyrosine kinase (RTK) inhibitors. RTKs efficiently target multiple receptors, including the Ron transmembrane receptor, whose activation leads to increased survival, migration, and angiogenesis through signaling pathways such as PI3K/Akt and NF-κB. Ron overexpression is correlated with increased metastasis and poor outcomes in patients. The only ligand for Ron is hepatocyte growth factor-like protein (HGFL), which is an endocrine factor secreted into the circulation from the liver. Published reports demonstrated that ectopic overexpression of HGFL in cancer cells leads to increased metastasis. However, no studies have examined the role of endogenous HGFL in Ron activation during tumor development and metastasis. We sought to test the hypothesis that HGFL is required for Ron receptor activation and mammary tumorigenesis. We utilized mice with mammary-specific Ron overexpression (MMTV-Ron), which develop mammary tumors with 100% ...

TY - JOUR. T1 - Tumor profiling of co-regulated receptor tyrosine kinase and chemoresistant genes reveal different targeting options for lung and gastroesophageal cancers. AU - Wu, Jianzhong. AU - Li, Shuchun. AU - Ma, Rong. AU - Sharma, Ashok Kumar. AU - Bai, Shan. AU - Dun, Boying. AU - Cao, Haixia. AU - Jing, Changwen. AU - She, Jin-Xiong. AU - Feng, Jifeng. PY - 2016/1/1. Y1 - 2016/1/1. N2 - The expression of a number of genes can influence the response rates to chemotherapy while genes encoding receptor tyrosine kinases (RTKs) determine the response to most targeted cancer therapies currently used in clinics. In this study, we evaluated seven genes known to influence chemotherapeutic response (ERCC1, BRCA1, RRM1, TUBB3, STMN1, TYMS, and TOP2A) and five RTKs (EGFR, ERBB2, PDGFRB, VEGFR1 and VEGFR2) in non-small cell lung cancer (NSCLC) and esophagus cancer (EC) and the data are compared to gastric cancer (GC) data reported previously. We demonstrate significant differences in the expression ...

FUNCTION: This gene encodes a precursor protein that is proteolytically cleaved to yield an alpha chain and a beta chain which form a membrane-spanning heterodimer. The encoded protein belongs to a family of cell-surface receptor tyrosine kinases involved in signaling from the cell surface to the intracellular environment. The binding of the encoded protein to its ligand, macrophage-stimulating protein, mediates several biological activities including wound healing, tumor immunity, macrophage activation and hematopoiesis as well as cell growth, motility, survival and adhesion. The protein encoded by this gene also functions in early development and the macrophage-mediated inflammatory response. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013 ...

Evidence-based recommendations on crizotinib (Xalkori) for previously treated anaplastic lymphoma kinase-positive advanced non-small-cell lung cancer in adults

Evidence-based recommendations on crizotinib (Xalkori) for previously treated anaplastic lymphoma kinase-positive advanced non-small-cell lung cancer in adults

TY - JOUR. T1 - Biochemical basis for the functional switch that regulates hepatocyte growth factor receptor tyrosine kinase activation. AU - Sheth, Payal R.. AU - Hays, John L.. AU - Elferink, Lisa. AU - Watowich, Stanley. PY - 2008/4/1. Y1 - 2008/4/1. N2 - Ligand-induced dimerization of receptor tyrosine kinases (RTKs) modulates a system of linked biochemical reactions, sharply switching the RTK from a quiescent state to an active state that becomes phosphorylated and triggers intracellular signaling pathways. To improve our understanding of this molecular switch, we developed a quantitative model for hepatocyte growth factor receptor (c-MET) activation using parameters derived in large part from c-MET kinetic and thermodynamic experiments. Our model accurately produces the qualitative and quantitative dynamic features of c-MET phosphorylation observed in cells following ligand binding, including a rapid transient buildup of phosphorylated c-MET at high ligand concentrations. In addition, our ...

There are 6 clinical trials for anaplastic large cell lymphoma, ALK-negative, of which 6 are open and 0 are completed or closed. Of the trials that contain anaplastic large cell lymphoma, ALK-negative as an inclusion criterion, 2 are phase 1 (2 open), 1 is phase 1/phase 2 (1 open), and 3 are phase 2 (3 open). TNFRSF8, ALK, and CD7 are the most frequent gene inclusion criteria for anaplastic large cell lymphoma, ALK-negative clinical trials [3]. ...

The patients clinical features at presentation, diagnosis, treatment and follow-up data are summarized in Table 1. Three patients were male and two female and they ranged in age from 7 to 11 years old. They received solitary (cases # 1, 3, and 4) or multiple insect bites (cases # 2 and 5). Four of them (cases # 1, 2, 3, 5) presented with persistent or growing skin lesions at the site of the bite. Satellite lymphadenopathy developed a few weeks after the bite in two cases (cases # 1 and 2). In one case (# 4), supraclavicular lymphadenopathy, which occurred 1 month after a neck bite, was the presenting symptom. All patients received antibiotics or steroids with no response in four cases (# 1, 2, 3 and 4) and a partial response in one case (case # 5). Four patients had fever at the time of diagnosis and two of the patients general condition deteriorated with weight loss, asthenia, and pulmonary signs (cases # 1 and 4). In one case (# 4), the nature of the insect bite was clearly identified as ...

cDNA, FLJ94334, Homo sapiens growth arrest-specific 2 (GAS2), mRNA (Growth arrest-specific 2, isoform CRA_a) contains a PF00307 domain.. cDNA, FLJ94334, Homo sapiens growth arrest-specific 2 (GAS2), mRNA (Growth arrest-specific 2, isoform CRA_a) contains a PF02187 domain.. cDNA, FLJ94334, Homo sapiens growth arrest-specific 2 (GAS2), mRNA (Growth arrest-specific 2, isoform CRA_a) is proteolytically cut by caspase-7 (C14.004) cleavage. SRVD-GKTS.. cDNA, FLJ94334, Homo sapiens growth arrest-specific 2 (GAS2), mRNA (Growth arrest-specific 2, isoform CRA_a) is proteolytically cut by caspase-3 (C14.003) cleavage. SRVD-GKTS.. ...

The envelope (Env) protein of jaagsiekte sheep retrovirus (JSRV) can transform cells in culture and is likely to be the main factor responsible for lung cancer induction by JSRV in animals. A recent report indicates that the epithelial-cell transforming activity of JSRV Env depends on activation of the cell-surface receptor tyrosine kinase Mst1r (called RON for the human and Stk for the rodent orthologs). In the immortalized line of human epithelial cells used (BEAS-2B cells), the virus receptor Hyal2 was found to bind to and suppress the activity of RON. When Env was expressed it bound to Hyal2 causing its degradation, release of RON activity from Hyal2 suppression, and activation of pathways resulting in cell transformation. Due to difficulty with reproducibility of the transformation assay in BEAS-2B cells, we have used more tractable rodent fibroblast models to further study Hyal2 modulation of RON/Stk transforming activity and potential effects of Hyal2 on RON/Stk activation by its natural ligand,

The gene encoding the mouse EphA8 receptor tyrosine kinase has been isolated from a mouse genomic library, and its complete genomic structure has been determined. This gene spans approximately 28 kb and consists of 17 exons. This gene structure is similar to the structure of the chick EphB2(Cek5) gene, except for one intron present between the first two exons encoding the EphA8 kinase domain. This difference may reflect an evolutionary divergence of the catalytic domain between EphA and EphB subgroup receptors. The site for transcription initiation has been mapped to the 19th nucleotide upstream from the translation start codon ATG. A feature of this gene is an unmethylated CpG island spanning exon 1 and the flanking sequence. The putative promoter of the EphA8 gene lacks a TATA box and contains multiple copies of the sequence GGGCGG, the core sequence of the putative Sp1-binding site. The 3.5-kb upstream genomic region containing part of the first exon showed strong promoter activity in ...

TY - JOUR. T1 - Recurrent MSCE116K mutations in ALK-negative anaplastic large cell lymphoma. AU - Luchtel, Rebecca A.. AU - Zimmermann, Michael T.. AU - Hu, Guangzhen. AU - Dasari, Surendra. AU - Jiang, Manli. AU - Oishi, Naoki. AU - Jacobs, Hailey K.. AU - Zeng, Yu. AU - Hundal, Tanya. AU - Rech, Karen L.. AU - Ketterling, Rhett P.. AU - Lee, Jeong Heon. AU - Eckloff, Bruce W.. AU - Yan, Huihuang. AU - Gaonkar, Krutika S.. AU - Tian, Shulan. AU - Ye, Zhenqing. AU - Kadin, Marshall E.. AU - Sidhu, Jagmohan. AU - Jiang, Liuyan. AU - Voss, Jesse. AU - Link, Brian K.. AU - Syrbu, Sergei I.. AU - Facchetti, Fabio. AU - Bennani, N. Nora. AU - Slager, Susan L.. AU - Ordog, Tamas. AU - Kocher, Jean Pierre. AU - Cerhan, James R.. AU - Ansell, Stephen M.. AU - Feldman, Andrew L.. PY - 2019/6/27. Y1 - 2019/6/27. N2 - Anaplastic large cell lymphomas (ALCLs) represent a relatively common group of T-cell non- Hodgkin lymphomas (T-NHLs) that are unified by similar pathologic features but demonstrate marked ...

We report the re-biopsied diagnosis of a patient with anaplastic lymphoma receptor tyrosine kinase (ALK)-positive lung adenocarcinoma successfully treated with ceritinib 450 mg/day taken with food following disease progression and gastrointestinal intolerance to crizotinib. A 74-year old female patient initially diagnosed with ALK-negative lung adenocarcinoma responded to initial standard chemotherapy. The patient was subsequently re-tested by next generation sequencing (NGS) and found to have ALK EIF2AK3-ALK fusion, and responded to crizotinib, but ultimately progressed and showed intolerance to this ALK inhibitor. She was then successfully treated with ceritinib 450 mg/day taken with food, has not suffered from any further gastrointestinal side-effects, and remains on ceritinib treatment after 12 months. Second-line ceritinib treatment, when administered at 450 mg/day with food, is both well tolerated and efficacious in a patient with previously treated lung adenocarcinoma who had discontinued

Fingerprint Dive into the research topics of Fes tyrosine kinase expression in the tumor niche correlates with enhanced tumor growth, angiogenesis, circulating tumor cells, metastasis, and infiltrating macrophages. Together they form a unique fingerprint. ...

The receptor tyrosine kinase AXL is thought to play a role in metastasis; however, the therapeutic efficacy of an AXL-targeting agent remains largely untested in metastatic disease. In this study, we defined AXL as a therapeutic target for metastatic ovarian cancer. AXL is primarily expressed in metastases and advanced-stage human ovarian tumors but not in normal ovarian epithelium. Genetic inhibition of AXL in human metastatic ovarian tumor cells is sufficient to prevent the initiation of metastatic disease in vivo. Mechanistically, inhibition of AXL signaling in animals with metastatic disease results in decreased invasion and matrix metalloproteinase activity. Most importantly, soluble human AXL receptors that imposed a specific blockade of the GAS6/AXL pathway had a profound inhibitory effect on progression of established metastatic ovarian cancer without normal tissue toxicity. These results offer the first genetic validation of GAS6/AXL targeting as an effective strategy for inhibition of

TOKYO, June 3, 2019 -- forgopro.com.ua, Ltd. (TOKYO: 4519) announced today that it filed an application for ALK Inhibitor, Alecensa® capsule 150 mg (generic name: alectinib) to MHLW for an additional indication of recurrent or refractory ALK fusion gene-positive anaplastic large cell lymphoma (ALK-positive ALCL). Alecensa obtained an orphan drug designation from the MHLW on May 30.. While chemotherapy is known to be effective for ALCL, there is a strong need for development of new therapeutic options since recurrent ALCL often carries a poor prognosis, said Dr. Yasushi Ito, Chugais Executive Vice President, Co-Head of Project & Lifecycle Management Unit. We hope that we can contribute to improving prognosis of these patients with the use of Alecensa that has the possibility of becoming a promising molecular target drug for ALK-positive ALCL.. This filing is based on the results from the investigator initiated study (the ALC-ALCL study) started in May 2015. The study has been conducted as a ...

0022] In detail the invention refers to: [0023] a pharmaceutical composition comprising an agent or agents having [0024] (i) at least one receptor tyrosine kinase blocking/inhibiting specificity and [0025] (ii) at least one angiogenesis blocking/inhibiting specificity, wherein said agent or agents is/are not a cytokine immunoconjugate, optionally together with a pharmaceutically acceptable carrier, diluent or recipient; [0026] as a first alternative, a pharmaceutical comprising [0027] (i) at least one agent having a receptor tyrosine kinase blocking specificity, and [0028] (ii) at least one agent having an angiogenesis inhibiting specificity; [0029] as a second alternative, a pharmaceutical composition, comprising an agent having a receptor tyrosine kinase blocking specificity as well as an angiogenesis inhibiting specificity. [0030] corresponding compositions further comprising at least one cytotoxic, preferably chemotherapeutic agent; [0031] in more detail, a pharmaceutical composition, ...

TY - JOUR. T1 - A receptor tyrosine kinase cDNA isolated from a population of enriched primitive hematopoietic cells and exhibiting close genetic linkage to c-kit. AU - Matthews, William. AU - Jordan, Craig T.. AU - Gavin, Marc. AU - Jenkins, Nancy A.. AU - Copeland, Neal G.. AU - Lemischka, Ihor R.. PY - 1991/10/15. Y1 - 1991/10/15. N2 - We have cloned a receptor tyrosine kinase cDNA, designated fetal liver kinase 1 (Flk-1), from mouse cell populations enriched for hematopoietic stem and progenitor cells. Sequence analysis of this clone reveals strong homology to the c-Kit subfamily of receptor kinases, and in particular to the Flt gene product. Chromosomal mapping shows that the Flk-1, Kit, and Pdgfra genes are closely linked. Flk-1 mRNA is expressed in primitive and more mature hematopoietic cells as well as in a wide variety of nonhematopoietic tissues.. AB - We have cloned a receptor tyrosine kinase cDNA, designated fetal liver kinase 1 (Flk-1), from mouse cell populations enriched for ...

We show that generation of holes in the Drosophila embryo can substitute for the Tsl protein in the activation of the Torso Receptor Tyrosine Kinase (RTK) and t

Here, we show that DDR1 is a critical regulator of atherogenesis. Deletion of DDR1 attenuates plaque development and results in a substantial change in plaque composition, including an early increase in extracellular matrix content and decreased macrophage accumulation. Ultimately, the plaques in DDR1-deficient mice are smaller and exhibit features consistent with greater stability.. We observed marked acceleration of fibrillar collagen and elastin accumulation in the plaques from the Ddr1−/−;Ldlr−/− mice. The observation of increased matrix accumulation with decreased lesion size may seem counterintuitive. However, it is important to understand that the matrix does not simply add bulk to the plaque; matrix molecules can influence cell behavior. For example, fibrillar collagens and intact elastin have been shown to inhibit SMC proliferation and migration.6,22-25 Furthermore, fibrillar collagen inhibits, whereas monomeric collagen potentiates macrophage MMP production,26 thereby affecting ...

The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to BGB324 for the treatment of acute myeloid leukemia (AML). BGB324 is a first-in-class, highly selective small-molecule inhibitor of the Axl receptor tyrosine kinase. It blocks the epithelial-mesenchymal transition (EMT), which is a key driver in drug-resistance and metastasis.. Earlier this month BerGenBio announced that the first patient has been dosed in its multicenter phase Ib trial of BGB324 in patients with AML. The two-part trial will primarily investigate the safety and tolerability of BGB324 when administered as a single agent and in combination with a standard-of-care drug (cytarabine). Secondary endpoints will also explore evidence of clinical response and assess novel biomarkers.. The FDA grants Orphan Drug designation to development-stage novel therapeutics that are intended for use in treating rare diseases and medical conditions that affect fewer than 200,000 patients in the United States. ■. ...

Leukocyte receptor tyrosine kinase is an enzyme that in humans is encoded by the LTK gene. The protein encoded by this gene is a member of the ALK/LTK receptor family of receptor tyrosine kinases (RTKs) whose ligand is unknown. Closely related to the insulin receptor family of RTKs. Tyrosine-specific phosphorylation of proteins is a key to the control of diverse pathways leading to cell growth and differentiation. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene. LTK has been shown to interact with IRS-1, Shc, and PIK3R1. GRCh38: Ensembl release 89: ENSG00000062524 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000027297 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Maru Y, Hirai H, Takaku F (May 1990). Human ltk: gene structure and preferential expression in human leukemic cells. Oncogene Res. 5 (3): 199-204. PMID 2320375. Entrez Gene: LTK leukocyte tyrosine kinase. Lopes SS, Yang X, Müller J, ...

555 The Macrophage-Stimulating Protein receptor aka. MSP-R or RON belongs to the c-MET family of receptor tyrosine kinases. The ligand for c-MET - Hepatocyte Growth Factor (HGF) as well as RONs ligand, MSP are members of the kringle-domain plasminogen-related protein family. As its name implies, MSP was originally found to stimulate macrophages by a variety of means. For example, addition of MSP to certain RON-expressing macrophages induced shape changes, chemotaxis, macropinocytosis and phagocytosis. RON was also found to be expressed in epithelial cells such as keratinocytes where MSP was shown to phosphorylate RON and activate a number of signaling pathways that elicited cell adhesion/motility, anti-apoptotic and proliferative responses. Within the last few years, however, over-expression of RON has been observed in several epithelial tumors and cell lines (ex. colon, breast and lung). In addition, the oncogenic potential of RON was recently demonstrated following its overexpression in ...

The role of Raf and MAPK (mitogen-activated protein kinase) during the maturation of Xenopus oocytes was investigated. Treatment of oocytes with progesterone resulted in a shift in the electrophoretic mobility of Raf at the onset of germinal vesicle breakdown (GVBD), which was coincident with the activation of MAPK. Expression of a kinase-defective mutant of the human Raf-1 protein (KD-RAF) inhibited progesterone-mediated MAPK activation. MAPK activation was also inhibited by KD-Raf in oocytes expressing signal transducers of the receptor tyrosine kinase (RTK) pathway, including an activated tyrosine kinase (Tpr-Met), a receptor tyrosine kinase (EGFr), and Ha-RasV12. KD-RAF completely inhibited GVBD induced by the RTK pathway. In contrast, KD-RAF did not inhibit GVBD and the progression to Meiosis II in progesterone-treated oocytes. Injection of Mos-specific antisense oligodeoxyribonucleotides inhibited MAPK activation in response to progesterone and Tpr-Met, but failed to inhibit these events ...

Background Several little receptor tyrosine kinase inhibitors (RTKI) have entered medical cancer trials alone and in conjunction with radiotherapy or chemotherapy. cells had been employed. LEADS TO fibroblasts, rays markedly triggered PDGF signaling as recognized by improved PDGFR phosphorylation that was potently inhibited by SU9518. In fibroblast clonogenic assay, SU9518 decreased PDGF activated fibroblast success by 57%. Also, SU9518 potently inhibited fibroblast and endothelial cell proliferation. In the co-culture model, rays of endothelial cells and fibroblast cells considerably activated proliferation of non irradiated fibroblasts and vice versa. Significantly, the RTK inhibitor considerably inhibited this paracrine buy 838818-26-1 radiation-induced fibroblast and endothelial cell activation. Summary Radiation-induced autocrine and paracrine PDGF signaling takes on an important part in fibroblast and endothelial cell proliferation. SU9518, a PDGFR tyrosine kinase inhibitor, decreases ...

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that it has received a second Breakthrough Therapy Designation (BTD) from the United States Food and Drug Administration (FDA) for its ALK inhibitor, Alecensa (alectinib). The latest BTD was granted for the treatment of adult patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) who have not received prior treatment with an ALK inhibitor.. The J-ALEX study that supports the second Breakthrough Designation for Alecensa showed superior efficacy versus the standard of care, crizotinib, in Japanese people with advanced ALK-positive disease, said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. The decision by the FDA to grant a second breakthrough therapy designation is recognition of the clinically meaningful improvement in efficacy and safety that Alecensa brings to the care of people with advanced ALK-positive lung cancer who have not received prior treatment with ...

The Met family of receptor tyrosine kinases (RTKs) contains two members in mammals, referred to as Met and Ron. Met is the receptor for hepatocyte growth factor/scatter factor (HGF/SF), while Ron is the receptor for macrophage stimulating protein (MSP).. In the adult, Met is predominantly expressed in epithelial and endothelial cells. Met regulates diverse cellular processes including cell scattering, proliferation and survival. It is involved in organ regeneration following kidney and liver damage. The Met and Ron receptors are essential for embryonic development as Met-/- and Ron-/- embryos die at E14.5-16.5 and E3.5, respectively. HGF/Met signaling is required for the development of the placenta, the liver and nervous system as well as the migration of myogenic precursor cells.. The Ron receptor is expressed in lineages of hematopoietic origin, in some epithelial cells, in cells of neuro-ectodermal origin and in osteoclasts. Ron is essential for embryonic implantation and is involved in a ...

phdthesis{7134a3c6-9b42-4596-bd81-007d9d912cd4, author = {LINDBLAD, OSCAR}, isbn = {978-91-7619-244-3}, language = {eng}, publisher = {Lund University: Faculty of Medicine}, school = {Lund University}, title = {FLT3 and KIT in acute myeloid leukemia. Translational studies on oncogenic signaling from receptor tyrosine kinases. : Translational studies on oncogenic signaling from receptor tyrosine kinases}, url = {https://lup.lub.lu.se/search/ws/files/7593560/FLT3_and_KIT_in_Acute_Myeloid_Leukemia.pdf}, year = {2016 ...

In search of oncogenic mechanisms and drivers affecting therapy resistance in breast cancer, we discovered is discovered to be portrayed in a subset of breasts malignancies highly. which it was proven to undergo speedy tyrosine phosphorylation in response to insulin9,10. IRSs are cytoplasmic scaffolding protein that action as indication transmitters between multiple receptor tyrosine kinases (RTK), including the insulin and IGF1 receptors, and many various other Src homology 2 (SH2) domain-containing protein (analyzed in refs 7, 11). On holding ligand-activated RTKs, many tyrosine residues in the huge C-terminal area of IRSs are phosphorylated. These phosphorylated tyrosine sites can serve as holding sites for downstream cytoplasmic SH2-filled with effector protein eventually, including g85 and GRB2, leading to the account activation of the MAPK/ERK and PI3T/AKT signalling paths, respectively (analyzed in refs 5, 11, 12). In addition, it provides been reported that phosphorylation of two ...

In search of oncogenic mechanisms and drivers affecting therapy resistance in breast cancer, we discovered is discovered to be portrayed in a subset of breasts malignancies highly. which it was proven to undergo speedy tyrosine phosphorylation in response to insulin9,10. IRSs are cytoplasmic scaffolding protein that action as indication transmitters between multiple receptor tyrosine kinases (RTK), including the insulin and IGF1 receptors, and many various other Src homology 2 (SH2) domain-containing protein (analyzed in refs 7, 11). On holding ligand-activated RTKs, many tyrosine residues in the huge C-terminal area of IRSs are phosphorylated. These phosphorylated tyrosine sites can serve as holding sites for downstream cytoplasmic SH2-filled with effector protein eventually, including g85 and GRB2, leading to the account activation of the MAPK/ERK and PI3T/AKT signalling paths, respectively (analyzed in refs 5, 11, 12). In addition, it provides been reported that phosphorylation of two ...

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Our new finding of the dose‐dependent shift of signaling modes by a GPCR has several implications. G‐protein‐dependent signaling and G‐protein‐independent signaling are related by their different sensitivity to concentrations of the same agonist. The G‐protein‐dependent signaling of GPCRs is similar to receptor tyrosine kinase signaling through the small GTPase Ras. The G protein‐independent signaling of GPCRs can be compared to cytokine JAK-STAT signaling, in which non‐receptor tyrosine kinases are directly coupled to membrane receptors. Also, it is interesting to note that some seven‐transmembrane receptors, such as Smoothened in Hedgehog gradient signaling, mainly use their C‐terminal tails to directly interact with downstream signaling molecules without the participation of G proteins (Lum and Beachy, 2004). Both the JAK-STAT and the Smoothened pathways result in activation of latent cytoplasmic transcription factors. Src could mediate GPCR‐responsive changes in gene ...

Mad1 (encoded by the gene mxd1), a member of the Myc/Mad/Max family known as bHLH/LZip proteins (1, 2), is recognized as an important cellular antagonist of Myc (1, 2). Mad1 antagonizes Myc function by recruiting Max and the mSin3 repressor complex to Myc-responsive elements, directly competing with the Myc-Max dimer for access to transcriptional sites (1, 2). The half-life of Mad1 protein, like that of Myc protein, is very short (1), and the levels of Mad1 are tightly regulated during cell proliferation and differentiation (2). In contrast, the levels of Max protein were found to be constitutive under different conditions (3, 4). Therefore, because both Myc and Mad1 compete for Max (1), the availability of Max to Myc is profoundly dependent on the expression levels of Mad1 protein (and vice versa).. PtdIns3 kinase (PI3K) is activated in response to mitogen stimulation of multiple receptor tyrosine kinases and G protein-coupled receptors. PI3K phosphorylates phosphatidylinositol-4, ...

Lenvima, a kinase inhibitor, blocks certain proteins that help cancer cells grow and divide Read More.... This past week the U.S. Food and Drug Administration (FDA) approved Eisais Lenvima (lenvatinib), an oral multiple receptor tyrosine kinase (RTK) inhibitor for the treatment of progressive, differentiated thyroid cancer (DTC) in patients whose disease progressed despite receiving radioactive iodine therapy. DTC is a cancerous growth of the thyroid gland in the neck that helps to regulate the bodys metabolism. Study results showed Lenvima-treated participants lived a median of 18.3 months without their disease progressing (progression-free survival), compared to a median of 3.6 months for participants who received a placebo. Lenvima was approved under the FDAs priority review program.. ...

The combination of lenvatinib-a multiple receptor tyrosine kinase (RTK) inhibitor-plus everolimus-a mammalian target of rapamycin (mTOR) inhibitor-significantly improved clinical outcomes versus everolimus monotherapy in a phase 2 clinical study of metastatic renal cell carcinoma (RCC).

The investigators propose to conduct a retrospective study of single agent ceritinib in patients with previously untreated anaplastic lymphoma kinase (ALK)

TY - JOUR. T1 - The cytosolic domain of protein-tyrosine kinase 7 (PTK7), generated from sequential cleavage by a disintegrin and metalloprotease 17 (ADAM17) and γ-secretase, enhances cell proliferation and migration in colon cancer cells. AU - Na, Hye Won. AU - Shin, Won Sik. AU - Ludwig, Andreas. AU - Lee, Seung Taek. PY - 2012/7/20. Y1 - 2012/7/20. N2 - Protein-tyrosine kinase 7 (PTK7) is a member of the defective receptor protein-tyrosine kinases and is known to function as a regulator of planar cell polarity during development. Its expression is up-regulated in some cancers including colon carcinomas. A 100-kDa fragment of PTK7 was detected in the culture media from colon cancer cells and HEK293 cells. The shed fragment was named sPTK7-Ig1-7 because its molecular mass was very similar to that of the entire extracellular domain of PTK7 that contains immunoglobulin-like loops 1 to 7 (Ig1-7). The shedding of sPTK7-Ig1-7 was enhanced by treatment with phorbol 12-myristate 13-acetate. In ...

In single-group studies, chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) have been associated with marked clinical responses to crizotinib, an oral tyrosine kinase inhibitor targeting ALK. Whether crizotinib is superior to standard chemotherapy with respect to efficacy is unknown. We conducted a phase 3, open-label trial comparing crizotinib with chemotherapy in 347 patients with locally advanced or metastatic ALK-positive lung cancer who had received one prior platinum-based regimen. Patients were randomly assigned to receive oral treatment with crizotinib (250 mg) twice daily or intravenous chemotherapy with either pemetrexed (500 mg per square meter of body-surface area) or docetaxel (75 mg per square meter) every 3 weeks. Patients in the chemotherapy group who had disease progression were permitted to cross over to crizotinib as part of a separate study. The primary end point was progression-free survival. The median progression-free survival was 7.7 months in the ...

Inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases 4-[(4-Fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline (AZD2171; Cediranib)

Signaling by receptor tyrosine kinases (RTKs) involves ligand-induced dimerization of receptors within the plasma membrane, triggering subsequent downstream signaling events. Although the transmembrane domains play an important role in dimerization, the importance of their interactions in transmembrane signaling is not clearly understood. Here, I highlight recent research that describes the intrinsic propensity of the single transmembrane domains of all 58 human RTKs to self-interact and suggest that these interactions could be exploited for designing peptides to inhibit signaling through these receptors. Such interceptor peptides would be potentially valuable as therapeutic tools for treating disease symptoms caused by excessive or ectopic RTK signaling.. ...

Activating KRAS mutations are commonly seen in 40% to 50% of human CRC (13). Although the prognostic role of such mutations is controversial, it is evident that they are powerful positive predictors for resistance to treatment with anti-EGFR therapies, such as cetuximab or panitumumab (14, 15). Because of the central role for KRAS in EGFR and other receptor tyrosine kinase signaling pathways during CRC carcinogenesis (16), robust KRAS-specific treatments are desperately needed for effective CRC treatment. As such efforts have been widely unsuccessful to date (17), the development of novel therapeutic approaches for treatment of KRAS-mutant CRC is a critical unmet clinical need.. Despite the identification of many candidate drug compounds during preclinical discovery efforts, the subsequent rate of success through the clinical trial pipeline is abysmal (18). Traditional preclinical drug discovery platforms often rely on genetically undefined and highly passaged human tumor cell lines. The in ...

In conclusion, osteopontin, a chemotactic protein with cytokine-like properties was found to be up-regulated in muscle injury caused by B. lanceolatus (fer-de-lance) snake. The upregulation of OPN occurred during the acute stage of inflammation and during myogenic cell proliferation and … Continue reading →. ...

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Molecular therapies target key functional molecules in order to halter viable operation of cancer cells. Receptor tyrosine kinases (RTKs) constitute attractive targets, as quite often their abnormal signaling has been associated with tumor development and growth. Overexpression of growth factor receptors, including IGF, EGF, TGF-α, SCF and PDGF receptors, has been associated with poor prognosis in breast cancer. Therefore, a number of RTKs are already targets for novel designed drugs, which involve tyrosine kinase inhibitors and monoclonal antibodies. Despite the fact that c-Kit and PDGF-R have been effective targets in a number of cancers, the experimental results in breast have not yet clarified their importance. The expression and function of c-Kit in breast cancer is a quite controversial subject. Several studies propose that the loss of c-Kit expression has been associated with tumor progress, whereas other reports indicate not only its expression but also the implication of c-Kit in ...

The gene fusion is common in androgen receptor (AR) positive prostate cancers yet its function remains poorly understood. fusion (Shah and Chinnaiyan 2009 positive PC cells we performed a pooled short hairpin RNA (shRNA) screen in and AR-positive VCaP prostate cancer cells using ERG-negative 22Rv1 cells as a control (Materials and methods). The shRNA pool … [Read more…]. ...