IL-2-induced signal transduction: involvement of tyrosine kinase and IL-2 receptor gamma chain.
We previously established a monoclonal antibody, TU11 mAb, which is specific for human IL-2 receptor (IL-2R) beta chain (p75) and does not inhibit IL-2-binding to IL-2R beta. Using TU11 mAb, we first demonstrated the existence of a third component, p64, of IL-2R, tentatively named the gamma chain of IL-2R. TU11 mAb precipitated not only the beta chain but also the alpha and gamma chains in the lysates of cells bearing the high-affinity IL-2R in the presence of IL-2 without any chemical crosslinker. The gamma chain was also detected in lymphoid MOLT alpha beta and MOLT beta cells, which were stably transfected with both alpha and beta cDNA, and with beta cDNA alone, respectively, but not in fibroblastoid COS alpha beta and COS beta cells, which were stably transfected with both alpha and beta cDNA, and with beta cDNA alone, respectively. Furthermore, IL-2-mediated growth signals were transduced in the lymphoid transfectant cells but not in the fibroblastoid transfectant cells, suggesting the possibility that the gamma chain along with the beta chain has an essential role in the transduction of IL-2-mediated growth signals. Using TU11 mAb, we secondly demonstrated that IL-2 rapidly induces tyrosine phosphorylation of both the beta and gamma chains in an IL-2-dose-dependent manner. The tyrosine phosphorylation of beta and gamma chains were also detected in the lymphoid transfectant cells but not in the fibroblastoid transfectant cells, indicating the correlation between tyrosine kinase activation and IL-2-mediated growth signaling. The beta chain was phosphorylated in in vitro on serine, threonine and tyrosine residues, but the gamma chain was phosphorylated in in vitro predominantly on tyrosine residues, suggesting the possibility that the gamma chain itself is a tyrosine kinase molecule.
Sugamura
K
K
Department of Microbiology, Tohoku University School of Medicine, Sendai, Japan.
Takeshita
T
T
Asao
H
H
Kumaki
S
S
Ohbo
K
K
Ohtani
K
K
Nakamura
M
M
D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D010446:Peptide Fragments / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D007376:Interleukin-2; D010446:Peptide Fragments; D011505:Protein-Tyrosine Kinases