title: Tyk2 mutation homologous to V617F Jak2 is not found in essential thrombocythaemia, although it induces constitutive signaling and growth factor independence.
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.
authors.affiliation: The First Department of Internal Medicine, Kyushu University Hospital, 3-1-1 Maidashi, Fukuoka, Fukuoka, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Shide
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shimoda
authors.forename: Kenjirou
authors.initials: K
authors.lastname: Kamezaki
authors.forename: Haruko
authors.initials: H
authors.lastname: Kakumitsu
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumano
authors.forename: Akihiko
authors.initials: A
authors.lastname: Numata
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Ishikawa
authors.forename: Katsuto
authors.initials: K
authors.lastname: Takenaka
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsuda
authors.forename: Mine
authors.initials: M
authors.lastname: Harada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured / Q000187:drug effects; D005260:Female; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases; D008297:Male; D051379:Mice; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009196:Myeloproliferative Disorders / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D053634:TYK2 Kinase / Q000235:genetics* / Q000378:metabolism; D013920:Thrombocythemia, Essential / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D007377:Interleukin-3; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; D008156:Luciferases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D053634:TYK2 Kinase; C070139:TYK2 protein, human