A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia.
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.
Lacronique
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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.
Boureux
A
A
Valle
V D
VD
Poirel
H
H
Quang
C T
CT
Mauchauffé
M
M
Berthou
C
C
Lessard
M
M
Berger
R
R
Ghysdael
J
J
Bernard
O A
OA
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
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