Induction of late activation events by Igbeta signaling subunit of B-cell receptor in Jurkat T-cell without tyrosine phosphorylation.
T-lymphocyte activation consists of multiple intracellular signaling events, eventually leading to cellular proliferation by the control of cytokine gene expression and the acquisition of diverse effector function. To investigate the functional specificity of ITAM (Immunoreceptor Tyrosine-based Activation Motif), chimeric molecules CD8-zeta, CD8-Igalpha, CD8-Igbeta, which contain the extracellular and transmembrane domains of the human CD8alpha molecule and the cytoplasmic tail of T-cell receptor (TcR) chain, Igalpha or Igbeta subunit of B-cell receptor, respectively, were stably expressed in a Jurkat cell line. Upon stimulation with anti-CD8 mAb OKT8, CD8-zeta and CD8-Igalpha chimeric proteins induced tyrosine phosphorylation of various cytoplasmic substrates as seen in TcR stimulation. They were also capable of stimulating IL-2 gene expression in a NF-AT dependent manner and inducing CD69 expression on the surface. However, stimulation of CD8-Igbeta can induce activation of CD69 surface expression and IL-2 gene expression equivalent to the level by CD8-Igalpha and CD8-zeta without induction of the tyrosine phosphorylation of intracellular signaling molecules. These results suggested that some of signaling chains containing ITAM may utilize a signal pathway without substrate tyrosine phosphorylation during T-cell activation leading to the IL-2 secretion.
Lim
J H
JH
Department of Biotechnology, College of Engineering and Bioproducts Research Center, Yonsei University, Seoul, Korea.
Kim
S W
SW
Song
Y S
YS
Lee
S K
SK
D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics; D051925:CD79 Antigens; D016827:CD8 Antigens / Q000235:genetics; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D019169:Jurkat Cells; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D051925:CD79 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D037181:Lectins, C-Type; D008565:Membrane Proteins; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D014443:Tyrosine; D000099192:CD69 Antigens; C497881:CD79A protein, human; C497883:CD79B protein, human; C054979:antigen T cell receptor, zeta chain