Identification of Elf-1 and B61 as high affinity ligands for the receptor tyrosine kinase MDK1.

Abstract:

:Mouse Developmental Kinase 1 (MDK1) is a receptor tyrosine kinase of the eck/eph subfamily expressed in a variety of tissues during early mouse embryogenesis. To obtain further insight into the function of MDK1, we determined identity and localisation of its physiological ligand(s). Staining whole embryos with fusion proteins between the extracellular domain of MDK1 and human secreted alkaline phosphatase revealed areas of high receptor binding in the caudal mesencephalon, the frontal neocortex and the limb buds. This staining was sensitive to treatment with phosphatidylinositol-specific phospholipase C. Using Scatchard analysis, high affinity binding of Elf-1 (1.7 x 10(-10) M) and B61 (2.2 x 10(-10) M) towards MDK1 could be demonstrated. However, the transmembrane ligand Lerk2 displayed no measurable affinity for MDK1. Elf-1 and B61 bind to the three full-length MDK1 isoforms with similar dissociation constants. Slightly lower affinities were observed for the two truncated receptors MDK1-Tl and MDK1-T2. The activation of MDK1 with Elf-1 or B61 leads to the rapid autophosphorylation of MDK1 as well as tyrosine phosphorylation of an unknown 62 kDa phosphoprotein in Rat1 cells. These findings implicate MDK1 in patterning processes during early mouse embryogenesis and suggest MDK1 involvement in early organogenesis and midbrain development.

journal_name

Oncogene

journal_title

Oncogene

authors

Ciossek T,Ullrich A

doi

10.1038/sj.onc.1200800

subject

Has Abstract

pub_date

1997-01-09 00:00:00

pages

35-43

issue

1

eissn

0950-9232

issn

1476-5594

journal_volume

14

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • Induction of telomerase activity by UV-irradiation in Chinese hamster cells.

    abstract::Telomerase is a ribonucleoprotein whose activity has been detected in germline cells and in neoplastic and immortal cells. Telomerase compensates the telomere loss arising by the end replication problem by synthesizing telomeric repeats at the 3' end of the eukaryotic chromosomes. Telomerase is reactivated during canc...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201327

    authors: Hande MP,Balajee AS,Natarajan AT

    更新日期:1997-10-02 00:00:00

  • Ero1-L alpha plays a key role in a HIF-1-mediated pathway to improve disulfide bond formation and VEGF secretion under hypoxia: implication for cancer.

    abstract::Oxygen is the ultimate source of oxidizing power for disulfide bond formation, suggesting that under limiting oxygen proper protein folding might be compromised. We show that secretion of vascular endothelial growth factor (VEGF), a protein with multiple disulfide bonds, was indeed impeded under hypoxia and was partia...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208325

    authors: May D,Itin A,Gal O,Kalinski H,Feinstein E,Keshet E

    更新日期:2005-02-03 00:00:00

  • MiR-663, a microRNA targeting p21(WAF1/CIP1), promotes the proliferation and tumorigenesis of nasopharyngeal carcinoma.

    abstract::MicroRNAs (miRNAs) may function as either oncogenes or tumor suppressors in the malignant progression of different tumor types. MiR-663 was recently reported to be decreased and identified as a tumor suppressor in gastric cancer. We also verified its role in repressing cell proliferation of a gastric cancer cell line....

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.629

    authors: Yi C,Wang Q,Wang L,Huang Y,Li L,Liu L,Zhou X,Xie G,Kang T,Wang H,Zeng M,Ma J,Zeng Y,Yun JP

    更新日期:2012-10-11 00:00:00

  • A combinatorial microRNA therapeutics approach to suppressing non-small cell lung cancer.

    abstract::Targeted cancer therapies, although often effective, have limited utility owing to preexisting primary or acquired secondary resistance. Consequently, agents are sometimes used in combination to simultaneously affect multiple targets. MicroRNA mimics are excellent therapeutic candidates because of their ability to rep...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2014.282

    authors: Kasinski AL,Kelnar K,Stahlhut C,Orellana E,Zhao J,Shimer E,Dysart S,Chen X,Bader AG,Slack FJ

    更新日期:2015-07-01 00:00:00

  • RalA suppresses early stages of Ras-induced squamous cell carcinoma progression.

    abstract::Ras proteins activate Raf and PI-3 kinases, as well as exchange factors for RalA and RalB GTPases. Many previous studies have reported that the Ral-signaling cascade contributes positively to Ras-mediated oncogenesis. Here, using a bioengineered tissue model of early steps in Ras-induced human squamous cell carcinoma ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2009.307

    authors: Sowalsky AG,Alt-Holland A,Shamis Y,Garlick JA,Feig LA

    更新日期:2010-01-07 00:00:00

  • Mammalian Mip/LIN-9 interacts with either the p107, p130/E2F4 repressor complex or B-Myb in a cell cycle-phase-dependent context distinct from the Drosophila dREAM complex.

    abstract::Mammalian Mip/LIN-9 is a cell cycle regulatory protein that is negatively regulated by CDK4/cyclin D. It has been demonstrated that Mip/LIN-9 collaborates with B-Myb during S and G(2)/M in the induction of cyclins A and B, and CDK1. The ortholog of Mip/LIN-9 in Drosophila, Mip130, is part of a large multisubunit prote...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210562

    authors: Pilkinton M,Sandoval R,Colamonici OR

    更新日期:2007-11-29 00:00:00

  • Overexpression of both catalytically active and -inactive cathepsin D by cancer cells enhances apoptosis-dependent chemo-sensitivity.

    abstract::The aspartic protease cathepsin D (cath-D) is a key mediator of induced-apoptosis and its proteolytic activity has been generally involved in this event. During apoptosis, cath-D is translocated to the cytosol. Because cath-D is one of the lysosomal enzymes that requires a more acidic pH to be proteolytically active r...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209221

    authors: Beaujouin M,Baghdiguian S,Glondu-Lassis M,Berchem G,Liaudet-Coopman E

    更新日期:2006-03-23 00:00:00

  • Induction of epithelial abnormalities that resemble human breast lesions by the expression of the neu/erbB-2 oncogene in reconstituted mouse mammary gland.

    abstract::We have developed a transplantation system that allows us to introduce oncogenes into mouse mammary epithelial cells in culture and then to reconstitute an epithelial tree in vivo from the genetically altered cells. Introduction of the neu oncogene, a transforming homologue of the human proto-oncogene c-erbB-2, produc...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Bradbury JM,Arno J,Edwards PA

    更新日期:1993-06-01 00:00:00

  • Phosphorylation of Helicobacter pylori CagA by c-Abl leads to cell motility.

    abstract::Helicobacter pylori induces a strong motogenic response in infected gastric epithelial host cells, which is enhanced by translocation of the pathogenic factor cytotoxin-associated gene A (CagA) into host cells via a specialized type IV secretion system. Once injected into the cytosol CagA is rapidly tyrosine phosphory...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210139

    authors: Poppe M,Feller SM,Römer G,Wessler S

    更新日期:2007-05-24 00:00:00

  • Intestinal cancer progression by mutant p53 through the acquisition of invasiveness associated with complex glandular formation.

    abstract::Tumor suppressor TP53 is frequently mutated in colorectal cancer (CRC), and most mutations are missense type. Although gain-of-functions by mutant p53 have been demonstrated experimentally, the precise mechanism for malignant progression in in vivo tumors remains unsolved. We generated ApcΔ716 Trp53LSL•R270H villin-Cr...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2017.194

    authors: Nakayama M,Sakai E,Echizen K,Yamada Y,Oshima H,Han TS,Ohki R,Fujii S,Ochiai A,Robine S,Voon DC,Tanaka T,Taketo MM,Oshima M

    更新日期:2017-10-19 00:00:00

  • Expression of the antimicrobial peptide cathelicidin in myeloid cells is required for lung tumor growth.

    abstract::Antimicrobial peptides, such as the cathelicidin LL-37/hCAP-18 and its mouse homolog cathelicidin-related antimicrobial peptide (CRAMP), are important effectors of the innate immune system with direct anti-bacterial activity. Cathelicidin is possibly involved in the regulation of tumor cell growth. The aim of this stu...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.248

    authors: Li D,Beisswenger C,Herr C,Schmid RM,Gallo RL,Han G,Zakharkina T,Bals R

    更新日期:2014-05-22 00:00:00

  • Sustained leukaemic phenotype after inactivation of BCR-ABLp190 in mice.

    abstract::Pharmacological inactivation of cancer genes or products is being used as a strategy for therapy in oncology. To investigate the potential role of BCR-ABLp190 cessation in leukaemia development, we generated mice carrying a tetracycline-repressible BCR-ABLp190 transgene. These mice were morphologically normal at birth...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209968

    authors: Pérez-Caro M,Gutierrez-Cianca N,González-Herrero I,López-Hernández I,Flores T,Orfao A,Sánchez-Martín M,Gutiérrez-Adán A,Pintado B,Sánchez-García I

    更新日期:2007-03-15 00:00:00

  • Upregulation of fibroblast growth factors and their receptors during multi-stage epidermal carcinogenesis in K14-HPV16 transgenic mice.

    abstract::Upregulation of acidic and basic fibroblast growth factors (FGF-1 and -2), and their cognate receptors FGFR-1 and -2, has been demonstrated in a variety of epithelial malignancies. However, the patterns of FGF/FGFR expression at specific stages of epithelial carcinogenesis have not been extensively characterized. In t...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Arbeit JM,Olson DC,Hanahan D

    更新日期:1996-11-07 00:00:00

  • Restoration of p53 expression sensitizes human papillomavirus type 16 immortalized human keratinocytes to CD95-mediated apoptosis.

    abstract::To understand the function of the individual oncogenes of HPV16 in modulating the cellular response to apoptogenic signals, we used human keratinocytes immortalized with either E6, E7 or E6/E7 oncoproteins as model system. Applying CD95 antibodies or recombinant CD95 ligand, only the E7-immortalized cells underwent ex...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204979

    authors: Aguilar-Lemarroy A,Gariglio P,Whitaker NJ,Eichhorst ST,zur Hausen H,Krammer PH,Rösl F

    更新日期:2002-01-10 00:00:00

  • PP2A-B56α controls oncogene-induced senescence in normal and tumor human melanocytic cells.

    abstract::Oncoprotein C-MYC is overexpressed in human metastatic melanomas and melanoma-derived cells where it is required for the suppression of oncogene-induced senescence (OIS). The genetic events that maintain high levels of C-MYC in melanoma cells and their role in OIS are unknown. Here we report that C-MYC in cells from s...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.339

    authors: Mannava S,Omilian AR,Wawrzyniak JA,Fink EE,Zhuang D,Miecznikowski JC,Marshall JR,Soengas MS,Sears RC,Morrison CD,Nikiforov MA

    更新日期:2012-03-22 00:00:00

  • Transformation by Hras(G12V) is consistently associated with mutant allele copy gains and is reversed by farnesyl transferase inhibition.

    abstract::RAS-driven malignancies remain a major therapeutic challenge. The two-stage 7,12-dimethylbenz(a)anthracene (DMBA)/12-o-tetradecanoylphorbol-13-acetate (TPA) model of mouse skin carcinogenesis has been used to study mechanisms of epithelial tumor development by oncogenic Hras. We used mice with an Hras(G12V) knock-in a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.489

    authors: Chen X,Makarewicz JM,Knauf JA,Johnson LK,Fagin JA

    更新日期:2014-11-20 00:00:00

  • AP-1--Introductory remarks.

    abstract::This issue attempts to give a 'state of the art' overview of the AP-1 transcription factor family, a fundamental class of transcriptional regulators. The AP-1 family consists of several bZIP (basic region leucine zipper) domain proteins, the Jun, the Fos, and the ATF subfamilies, which all have to dimerize before they...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204416

    authors: Wagner EF

    更新日期:2001-04-30 00:00:00

  • The amino-terminal half of pp59c-fyn contains sequences necessary for formation of a 75 kDa form and also repressive elements absent in pp60c-src.

    abstract::Members of the src family of tyrosine kinases are composed of amino acid sequences which can be divided into three regions: the unique amino-terminal 80 residues; the next 180 residues of conserved but non-catalytic sequence; and the catalytic carboxy-terminal half of the molecule. To characterize the elements that re...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Espino PC,Chou WY,Smith AE,Cheng SH

    更新日期:1992-02-01 00:00:00

  • CKIP-1 acts as a colonic tumor suppressor by repressing oncogenic Smurf1 synthesis and promoting Smurf1 autodegradation.

    abstract::Dysregulation of cellular signaling pathways can lead to colon cancer. However, research on the key signaling effectors or regulators in colon carcinogenesis is limited. Casein kinase-2 interacting protein-1 (CKIP-1; also known as PLEKHO1) is crucial during adult bone formation and is a promising drug target for osteo...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.340

    authors: Nie J,Liu L,Xing G,Zhang M,Wei R,Guo M,Li X,Xie P,Li L,He F,Han W,Zhang L

    更新日期:2014-07-10 00:00:00

  • Dominant negative Met reduces tumorigenicity-metastasis and increases tubule formation in mammary cells.

    abstract::Activation of the Met tyrosine kinase growth factor receptor by its ligand HGF/SF has been shown to increase in vitro invasiveness in epithelial cell lines. To study the effect of Met-HGF/SF signaling in breast cancer cells, we transfected met, hgf/sf and dominant negative (DN) forms of met into the poorly differentia...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203557

    authors: Firon M,Shaharabany M,Altstock RT,Horev J,Abramovici A,Resau JH,Vande Woude GF,Tsarfaty I

    更新日期:2000-05-11 00:00:00

  • Transcription of the RelB gene is regulated by NF-kappaB.

    abstract::RelA and RelB are two members of the NF-kappaB family that differ structurally and functionally. While RelA is regulated through its cytosolic localization by inhibitor proteins or IkappaB and not through transcriptional mechanisms, the regulation of RelB is poorly understood. In this study we demonstrate that stimuli...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204868

    authors: Bren GD,Solan NJ,Miyoshi H,Pennington KN,Pobst LJ,Paya CV

    更新日期:2001-11-22 00:00:00

  • Cytoplasmic localization of NPM in myeloid leukemias is dictated by gain-of-function mutations that create a functional nuclear export signal.

    abstract::Nucleophosmin (NPM) is a nucleus-cytoplasmic shuttling protein that is implicated in centrosome duplication, cell cycle progression and stress response. At the steady state, NPM localizes mainly in the nucleolus, where it forms a complex with different cellular proteins. One-third of acute myeloid leukemias (AML) are ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209453

    authors: Mariano AR,Colombo E,Luzi L,Martinelli P,Volorio S,Bernard L,Meani N,Bergomas R,Alcalay M,Pelicci PG

    更新日期:2006-07-20 00:00:00

  • GNAS(R201H) and Kras(G12D) cooperate to promote murine pancreatic tumorigenesis recapitulating human intraductal papillary mucinous neoplasm.

    abstract::Intraductal papillary mucinous neoplasm (IPMN), the most common pancreatic cystic neoplasm, is known to progress to invasive ductal adenocarcinoma. IPMNs commonly harbor activating somatic mutations in GNAS and KRAS, primarily GNAS(R201H) and KRAS(G12D). GNAS encodes the stimulatory G-protein α subunit (Gsα) that medi...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2015.294

    authors: Taki K,Ohmuraya M,Tanji E,Komatsu H,Hashimoto D,Semba K,Araki K,Kawaguchi Y,Baba H,Furukawa T

    更新日期:2016-05-05 00:00:00

  • SirT1-null mice develop tumors at normal rates but are poorly protected by resveratrol.

    abstract::The function of the class III histone deacetylase, Sir2, in promoting lifespan extension is well established in small model organisms. By analogy, SirT1, the mammalian orthologue of Sir2, is a candidate gene to slow down aging and forestall the onset of age-associated diseases. We have used SirT1-null mice to study th...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2009.147

    authors: Boily G,He XH,Pearce B,Jardine K,McBurney MW

    更新日期:2009-08-13 00:00:00

  • TBX3 promotes proliferation of papillary thyroid carcinoma cells through facilitating PRC2-mediated p57KIP2 repression.

    abstract::The T-box transcription factor TBX3 has been implicated in the patterning and differentiation of a number of tissues during embryonic development, and is overexpressed in a variety of cancers; however, the precise function of TBX3 in papillary thyroid carcinoma (PTC) development remains to be determined. In the curren...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-017-0090-2

    authors: Li X,Ruan X,Zhang P,Yu Y,Gao M,Yuan S,Zhao Z,Yang J,Zhao L

    更新日期:2018-05-01 00:00:00

  • miR-130a targets MET and induces TRAIL-sensitivity in NSCLC by downregulating miR-221 and 222.

    abstract::Non-small cell lung cancer (NSCLC) accounts for ∼80% of all lung cancers. Although some advances in lung cancer therapy have been made, patient survival is still quite poor. Two microRNAs, miR-221 and miR-222, upregulated by the MET proto-oncogene, have been already described to enhance cell survival and to induce TNF...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.260

    authors: Acunzo M,Visone R,Romano G,Veronese A,Lovat F,Palmieri D,Bottoni A,Garofalo M,Gasparini P,Condorelli G,Chiariello M,Croce CM

    更新日期:2012-02-02 00:00:00

  • A role for Janus kinases in crosstalk between ErbB3 and the interferon-alpha signaling complex in myeloma cells.

    abstract::Receptor crosstalk is an emerging and recurrent theme in cytokine and growth factor signaling; however, insight into the mechanism(s) underlying these interactions remains limited. Recently, we reported that crosstalk occurs between ErbB3 and the interferon alpha (IFN-alpha) signaling complex in the myeloma cell line ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207203

    authors: Walters DK,Jelinek DF

    更新日期:2004-02-12 00:00:00

  • The tumor suppressor p53 associates with gene coding regions and co-traverses with elongating RNA polymerase II in an in vivo model.

    abstract::Sequence-specific transcriptional regulators function by stably binding cognate DNA sequences followed by recruitment of both general and specialized factors to target gene promoters. The tumor suppressor p53 mediates its anti-oncogenic effect on cells by functioning as a sequence-specific regulator. p53 employs a sec...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210935

    authors: Balakrishnan SK,Gross DS

    更新日期:2008-04-24 00:00:00

  • Bloom's syndrome protein response to ultraviolet-C radiation and hydroxyurea-mediated DNA synthesis inhibition.

    abstract::Bloom's syndrome (BS) arises through mutations in both copies of the BLM gene that encodes a RecQ 3'-5' DNA helicase. BS patients are predisposed to developing all the cancers that affect the general population, and BS cells exhibit marked genetic instability. We showed recently that BLM protein contributes to the cel...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205246

    authors: Ababou M,Dumaire V,Lécluse Y,Amor-Guéret M

    更新日期:2002-03-27 00:00:00

  • Differential expression of DOC-1 in microsatellite-unstable human colorectal cancer.

    abstract::The precise genetic mechanism of malignant transformation in DNA mismatch repair deficient, microsatellite-unstable colorectal cancer (CRC) has yet to be elucidated. We employed cDNA microarray to identify patterns of gene expression among CRC cell lines and to compare directly lines with and without microsatellite in...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206609

    authors: Yuan Z,Sotsky Kent T,Weber TK

    更新日期:2003-09-18 00:00:00