Identification of a constitutively active mutant of JAK3 by retroviral expression screening.
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.
Choi
Young Lim
YL
Division of Functional Genomics, Jichi Medical University, 3311-1 Yakushiji, Shimotsukeshi, Tochigi 329-0498, Japan.
Kaneda
Ruri
R
Wada
Tomoaki
T
Fujiwara
Shin-Ichiro
S
Soda
Manabu
M
Watanabe
Hideki
H
Kurashina
Kentaro
K
Hatanaka
Hisashi
H
Enomoto
Munehiro
M
Takada
Shuji
S
Yamashita
Yoshihiro
Y
Mano
Hiroyuki
H
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
C507933:JAK3 protein, human; D053616:Janus Kinase 3