Protein tyrosine kinase Syk is associated with and activated by the IL-2 receptor: possible link with the c-myc induction pathway.
The IL-2 receptor (IL-2R) consists of three subunits, the IL-2R alpha, IL-2R beta, and IL-2R gamma chains. The IL-2-induced proliferative signals emanate from the cytoplasmic domains of IL-2R beta and IL-2R gamma, but the nature and function of the signaling molecules that transmit these signals are not fully understood. Here, we report that Syk protein tyrosine kinase (PTK) is physically associated with IL-2R in peripheral blood lymphocytes. cDNA expression studies further revealed that this association is critical for the IL-2-induced activation of Syk PTK, which occurs primarily via the serine-rich region of the IL-2R beta chain, which is essential for proliferative signal transmission. Furthermore, we provide evidence that in the hematopoietic cell line, BAF-B03, the activation of Syk PTK results in the induction of the c-myc gene, an event critical for the cell proliferation. Thus, Syk PTK may be a critical integral member of the signaling molecules engaged by the IL-2R.
Minami
Y
Y
Institute for Molecular and Cellular Biology Osaka University, Japan.
Nakagawa
Y
Y
Kawahara
A
A
Miyazaki
T
T
Sada
K
K
Yamamura
H
H
Taniguchi
T
T
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002461:Cell Line, Transformed; D002522:Chlorocebus aethiops; D018076:DNA, Complementary / Q000235:genetics; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D005786:Gene Expression Regulation; D016259:Genes, myc; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000201:enzymology*; D046911:Macromolecular Substances; D051379:Mice; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013552:Swine; D000072377:Syk Kinase; D014162:Transfection
D000911:Antibodies, Monoclonal; D018076:DNA, Complementary; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D016271:Proto-Oncogene Proteins c-myc; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse