title: Identification of a constitutively active mutant of JAK3 by retroviral expression screening.
abstract: To identify transforming genes in acute myeloid leukemia (AML) we here constructed a retroviral cDNA expression library from an AML patient, and then used this library to infect a mouse cell line 32Dcl3-mCAT. cDNA inserts of the cell clones which proliferated in the presence of granulocyte colony-stimulating factor were derived from JAK3 encoding a JAK3 mutant with a valine-to-alanine substitution at codon 674 and two additional amino acid substitutions. The transforming activity of JAK3(V674A) was confirmed by its introduction into 32Dcl3-mCAT. Sequencing of the original JAK3 cDNA derived from the patient, however, failed to detect the V674A mutation.
authors.affiliation: Division of Functional Genomics, Jichi Medical University, 3311-1 Yakushiji, Shimotsukeshi, Tochigi 329-0498, Japan.
authors.forename: Young Lim
authors.initials: YL
authors.lastname: Choi
authors.forename: Ruri
authors.initials: R
authors.lastname: Kaneda
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Wada
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Fujiwara
authors.forename: Manabu
authors.initials: M
authors.lastname: Soda
authors.forename: Hideki
authors.initials: H
authors.lastname: Watanabe
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kurashina
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hatanaka
authors.forename: Munehiro
authors.initials: M
authors.lastname: Enomoto
authors.forename: Shuji
authors.initials: S
authors.lastname: Takada
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mano
mesh_terms: D000208:Acute Disease; D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D002472:Cell Transformation, Viral; D003001:Cloning, Molecular; D015870:Gene Expression; D015723:Gene Library; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D053616:Janus Kinase 3 / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000235:genetics*; D051379:Mice; D009154:Mutation; D012190:Retroviridae / Q000235:genetics* / Q000378:metabolism
chemical_list: C507933:JAK3 protein, human; D053616:Janus Kinase 3