Similarities and differences in signal transduction by interleukin 4 and interleukin 13: analysis of Janus kinase activation.
The cytokines interleukin (IL) 4 and IL-13 induce many of the same biological responses, including class switching to IgE and induction of major histocompatibility complex class II antigens and CD23 on human B cells. It has recently been shown that IL-4 induces the tyrosine phosphorylation of a 170-kDa protein, a substrate called 4PS, and of the Janus kinase (JAK) family members JAK1 and JAK3. Because IL-13 has many functional effects similar to those of IL-4, we compared the ability of IL-4 and IL-13 to activate these signaling molecules in the human multifactor-dependent cell line TF-1. In this report we demonstrate that both IL-4 and IL-13 induced the tyrosine phosphorylation of 4PS and JAK1. Interestingly, although IL-4 induced the tyrosine phosphorylation of JAK3, we did not detect JAK3 phosphorylation in response to IL-13. These data suggest that IL-4 and IL-13 signal in similar ways via the activation of JAK1 and 4PS. However, our data further indicate that there are significant differences because IL-13 does not activate JAK3.
Keegan
A D
AD
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Johnston
J A
JA
Tortolani
P J
PJ
McReynolds
L J
LJ
Kinzer
C
C
O'Shea
J J
JJ
Paul
W E
WE
D000818:Animals; D001853:Bone Marrow; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D053613:Janus Kinase 1; D053616:Janus Kinase 3; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D018793:Interleukin-13; D007377:Interleukin-3; D011994:Recombinant Proteins; D015847:Interleukin-4; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507933:JAK3 protein, human; C507905:Jak1 protein, mouse; C507935:Jak3 protein, mouse; D053613:Janus Kinase 1; D053616:Janus Kinase 3