Interleukin 2-induced activation of JAK3: possible involvement in signal transduction for c-myc induction and cell proliferation.
We have investigated the role of JAK3 in interleukin 2 (IL-2)-induced signal transduction with a human T cell line, ED40515(-), lacking expression of the IL-2 receptor gamma chain and its sublines transfected with wild-type or mutant cDNAs of the IL-2 receptor gamma chain. Our results demonstrated that the membrane-proximal cytoplasmic region, encompassing the src homology region 2 (SH2)-like subdomain, of the gamma chain is essential for association and activation of JAK3. Furthermore, IL-2-induced activation of JAK3 paralleled induction of the c-myc gene and DNA synthesis but not induction of the c-fos and c-jun genes. These results support the hypothesis that JAK3 plays a pivotal role in the IL-2 receptor-mediated signals for cell growth.
Asao
H
H
Department of Microbiology, Tohoku University School of Medicine, Sendai, Japan.
Tanaka
N
N
Ishii
N
N
Higuchi
M
M
Takeshita
T
T
Nakamura
M
M
Shirasawa
T
T
Sugamura
K
K
D002455:Cell Division; D002461:Cell Line, Transformed; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D016259:Genes, myc; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000235:genetics; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects*
D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D015375:Receptors, Interleukin-2; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507933:JAK3 protein, human; D053614:Janus Kinase 2; D053616:Janus Kinase 3