IL-4 and IL-13 induce Lsk, a Csk-like tyrosine kinase, in human monocytes.
Lsk is a protein tyrosine kinase with homology to the COOH-terminal Src kinase (Csk). Unlike Csk that is ubiquitously expressed, Lsk has limited tissue distribution. Here we have examined the expression and regulation of Lsk and Csk in peripheral human monocytes. We have found that Lsk mRNA and protein were not expressed in resting monocytes but were induced by treatment with interleukin 4 (IL-4) or IL-13 but not by interferon gamma (IFN-gamma) or IL-2. In fact, IFN-gamma, but not IL-2, efficiently blocked Lsk induction by IL-4 or IL-13. In contrast, Csk was constitutively present in human monocytes and was upregulated by IFN-gamma but not by IL-4 or IL-13. These results suggest that despite their structural similarities, Lsk and Csk may play distinct regulatory roles in monocyte functions elicited by cytokines, with Lsk functioning specifically within the context of a Th2-type immune response.
Biological Carcinogenesis and Development Program, Program Resources, Inc./DynCorp., National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201.
T
T
Musso
L
L
Varesio
X
X
Zhang
T K
TK
Rowe
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P
Ferrara
J R
JR
Ortaldo
J J
JJ
O'Shea
D W
DW
McVicar
D015152:Blotting, Northern; D000081247:CSK Tyrosine-Protein Kinase; D002478:Cells, Cultured; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology*; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000302:isolation & purification; D016392:Proto-Oncogene Proteins pp60(c-src); D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D019061:src-Family Kinases
D018793:Interleukin-13; D007376:Interleukin-2; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; C085377:MATK protein, human; D016392:Proto-Oncogene Proteins pp60(c-src); D019061:src-Family Kinases; C000631346:CSK protein, human