Interleukin-1 induces protein tyrosine phosphorylation in T cells.
Interleukin (IL)-1 alpha activates multiple signal transmission pathways in the T helper type 2 cell line, D10A, and these pathways are linked to two separate IL-1 receptors (IL-1R). In the present report we show that IL-1 induces the activation of tyrosine kinase in these cells, leading to tyrosine phosphorylation of a subset of proteins of 38, 75, 97 and 115 kDa. This type of phosphorylation is prevented by a monoclonal antibody directed against the 80-kDa IL-1R and by tyrphostins which are specific inhibitors of tyrosine kinases. In addition, this inhibitor blocks IL-1-and IL-2-induced proliferation in D10A cells as well as the c-myc and c-myb proto-oncogene mRNA expression in response to IL-1. Interestingly, the inhibitor of cAMP-dependent kinase, H-8, only blocks IL-1-induced c-myb, but not c-myc mRNA expression. Altogether, our results demonstrate that the activation of a tyrosine kinase(s) is an early and major event that happens after IL-1/IL-1R interaction, leading to an increase in intracellular cAMP which results in c-myb and IL-5 mRNA expression. Independent of cAMP, by tyrosine phosphorylation of specific substrates IL-1 also induces c-myc and IL-6 mRNA expression and cellular proliferation.
Muñoz
E
E
Department of Pathology, Tufts Medical School, Boston.
Zubiaga
A
A
Huang
C
C
Huber
B T
BT
D000818:Animals; D001597:Benzylidene Compounds / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007375:Interleukin-1 / Q000502:physiology*; D007376:Interleukin-2 / Q000502:physiology; D015848:Interleukin-5 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D020598:Proto-Oncogene Proteins c-myb; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D012313:RNA / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000502:physiology; D017472:Receptors, Interleukin-1; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D020032:Tyrphostins
D001597:Benzylidene Compounds; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D007376:Interleukin-2; D015848:Interleukin-5; D015850:Interleukin-6; D009570:Nitriles; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D016271:Proto-Oncogene Proteins c-myc; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D020032:Tyrphostins; C075062:tyrphostin 11; D005576:Colforsin; C075061:tyrphostin 8; D012313:RNA; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases