title: A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia.
abstract: The Janus family of tyrosine kinases (JAK) plays an essential role in development and in coupling cytokine receptors to downstream intracellular signaling events. A t(9;12)(p24;p13) chromosomal translocation in a T cell childhood acute lymphoblastic leukemia patient was characterized and shown to fuse the 3' portion of JAK2 to the 5' region of TEL, a gene encoding a member of the ETS transcription factor family. The TEL-JAK2 fusion protein includes the catalytic domain of JAK2 and the TEL-specific oligomerization domain. TEL-induced oligomerization of TEL-JAK2 resulted in the constitutive activation of its tyrosine kinase activity and conferred cytokine-independent proliferation to the interleukin-3-dependent Ba/F3 hematopoietic cell line.
authors.affiliation: U 301 de l'Institut National de la Santé et de la Recherche Médicale and SD 401 No. 301 CNRS, Institut de Génétique Moléculaire, 27 rue Juliette Dodu, 75010 Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Lacronique
authors.forename: A
authors.initials: A
authors.lastname: Boureux
authors.forename: V D
authors.initials: VD
authors.lastname: Valle
authors.forename: H
authors.initials: H
authors.lastname: Poirel
authors.forename: C T
authors.initials: CT
authors.lastname: Quang
authors.forename: M
authors.initials: M
authors.lastname: Mauchauffé
authors.forename: C
authors.initials: C
authors.lastname: Berthou
authors.forename: M
authors.initials: M
authors.lastname: Lessard
authors.forename: R
authors.initials: R
authors.lastname: Berger
authors.forename: J
authors.initials: J
authors.lastname: Ghysdael
authors.forename: O A
authors.initials: OA
authors.lastname: Bernard
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001704:Biopolymers; D002455:Cell Division; D002460:Cell Line; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D007377:Interleukin-3 / Q000502:physiology; D053614:Janus Kinase 2; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008894:Milk Proteins; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D001704:Biopolymers; D004268:DNA-Binding Proteins; D007377:Interleukin-3; D053614:Janus Kinase 2; D008894:Milk Proteins; D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein; C108603:TEL-JAK2 fusion protein, human; C491568:TEL-JAK2 fusion protein, mouse; C507924:JAK2 protein, human; C507926:Jak2 protein, mouse