Regulation of JAK3 expression in human monocytes: phosphorylation in response to interleukins 2, 4, and 7.
The Janus family of kinases (JAKs) has been shown to be involved in the signal transduction of a number of cytokine receptors. Recently, we have cloned a novel JAK family member, JAK3, that is expressed in natural killer and activated T cells and is coupled functionally and physically to the interleukin 2 (IL-2) receptor in these cells. Here we report that JAK3 was expressed at low but detectable levels in human monocytes. In contrast, JAK3 expression was strongly induced during activation by interferon gamma (IFN-gamma) or lipopolysaccharide. Moreover, JAK3 became tyrosine phosphorylated in response to IL-2, IL-4, and IL-7 but not response to IFN-gamma or granulocyte/macrophage colony-stimulating factor. Together, these findings suggest that JAK3 is functionally important in activated monocytes and cells of the myeloid lineage and is involved in signaling responses of cytokines that use the common gamma-chain of the IL-2 receptor.
Musso
T
T
Biological Carcinogenesis and Development Program, Program Resources, Inc./DynCorp, Frederick, Maryland 21702-1201, USA.
Johnston
J A
JA
Linnekin
D
D
Varesio
L
L
Rowe
T K
TK
O'Shea
J J
JJ
McVicar
D W
DW
D002460:Cell Line; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D015851:Interleukin-7 / Q000494:pharmacology*; D053616:Janus Kinase 3; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D019089:Stem Cell Factor
D016298:Hematopoietic Cell Growth Factors; D007376:Interleukin-2; D015851:Interleukin-7; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3