title: The kinase defective EPHB6 receptor tyrosine kinase activates MAP kinase signaling in lung adenocarcinoma.
abstract: Decreased expression levels of EPHB6, a member of the receptor tyrosine kinases (RTKs), are associated with an increased risk of metastasis development in early stage non-small cell lung cancer (NSCLC). However, the signaling properties of the kinase-defective EPHB6 receptor are not well-understood. Here, we show that expression of EPHB6 in A549 lung adenocarcinoma cells led to phosphorylation of the MAP kinase ERK. Conversely, siRNA based knockdown of EPHB6 reversed ERK phosphorylation. Intriguingly, EPHB6-induced phosphorylation of ERK was uncoupled by activation of the Elk-1 transcriptional factor. These analyses suggest that kinase defective EPHB6 can lead to MAPK activation.
authors.affiliation: Department of Medicine, Hematology and Oncology, University of Münster, D-48129 Münster, Germany.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Etmar
authors.initials: E
authors.lastname: Bulk
authors.forename: Ping
authors.initials: P
authors.lastname: Ji
authors.forename: Antje
authors.initials: A
authors.lastname: Hascher
authors.forename: Steffen
authors.initials: S
authors.lastname: Koschmieder
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: Carsten
authors.initials: C
authors.lastname: Müller-Tidow
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics; D020935:MAP Kinase Signaling System; D010766:Phosphorylation; D034622:RNA Interference; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D036081:Receptors, Eph Family; D013997:Time Factors; D014162:Transfection; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism
chemical_list: C494112:ELK1 protein, human; D050807:ets-Domain Protein Elk-1; C106797:EPHB6 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D036081:Receptors, Eph Family; D048049:Extracellular Signal-Regulated MAP Kinases