Abstract
A single somatic mutation, V617F, in the pseudokinase domain of the Jak2 is the primary cause of many chronic myeloproliferative diseases. As valine 617 of Jak2 is conserved as valine 678 of Tyk2, we examined the effect of a homologous mutation in Tyk2 (V678F Tyk2) on cell growth. V678F Tyk2 augmented the transcriptional activity of Stat3 and Stat5. The expression of V678F Tyk2 in Ba/F3 cells induced autonomous cell growth and showed hyper-responsiveness to IL-3. Although V678F Tyk2 might cause MPD, no cases of ET patients lacking the V617F Jak2 mutation harbored the Tyk2 mutation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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Animals
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Blotting, Western
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Cell Proliferation
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Cells, Cultured / drug effects
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Female
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Humans
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Interleukin-3 / pharmacology
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Janus Kinase 2 / genetics*
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Janus Kinase 2 / metabolism
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Luciferases
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Male
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Mice
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Middle Aged
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Mutation / genetics*
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Myeloproliferative Disorders / genetics*
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STAT3 Transcription Factor / metabolism
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STAT5 Transcription Factor / metabolism
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Signal Transduction*
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TYK2 Kinase / genetics*
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TYK2 Kinase / metabolism
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Thrombocythemia, Essential / genetics*
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Transcription, Genetic
Substances
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Interleukin-3
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STAT3 Transcription Factor
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STAT3 protein, human
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STAT5 Transcription Factor
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Luciferases
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JAK2 protein, human
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Janus Kinase 2
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TYK2 Kinase
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TYK2 protein, human