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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Biopolymers
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Cell Division
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Cell Line
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Child, Preschool
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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ETS Translocation Variant 6 Protein
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Enzyme Activation
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Humans
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Interleukin-3 / physiology
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Janus Kinase 2
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Leukemia-Lymphoma, Adult T-Cell / genetics
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Leukemia-Lymphoma, Adult T-Cell / metabolism*
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Male
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Mice
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Milk Proteins*
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Molecular Sequence Data
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Oncogene Proteins, Fusion / chemistry
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Oncogene Proteins, Fusion / genetics
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Oncogene Proteins, Fusion / metabolism*
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Phosphorylation
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Protein-Tyrosine Kinases / chemistry
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism*
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Proto-Oncogene Proteins c-ets
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Proto-Oncogene Proteins*
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Repressor Proteins*
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STAT5 Transcription Factor
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Signal Transduction
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Trans-Activators / metabolism
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transfection
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Translocation, Genetic
Substances
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Biopolymers
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DNA-Binding Proteins
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Interleukin-3
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Milk Proteins
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Oncogene Proteins, Fusion
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-ets
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Repressor Proteins
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STAT5 Transcription Factor
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TEL-JAK2 fusion protein, human
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TEL-JAK2 fusion protein, mouse
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Trans-Activators
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Transcription Factors
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Protein-Tyrosine Kinases
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JAK2 protein, human
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Jak2 protein, mouse
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Janus Kinase 2